PROCEDURE FOR THE PRODUCTION OF BIOCATALYSTS BY IMMOBILIZATION OF ENZYMATICALLY ACTIVE ONE CELL MATERIAL

The invention concerns a procedure for the production of biocatalysts by immobilization of enzymatically active cell material out whole, intact native or if necessary before permeabilisierten cells or Zellfragrnenten and of them subcellulären particles and/or mixtures of whole naive cells with their cell fragments, subcellulären particles and all set free cell contents and/or - whole, individually interlaced and permeabilisierten cells, separation of the developed cell aggregates from the Reaküonsgemisch and washing with water or a buffer solution as well as if necessary further Permeabilisierung and/or mechanical Verfesägung. According to invention manufactured the biocatalysts are suitable for biotechnical transformations in industrial yardstick and make possible with diskonUnuierlicher or continuous Veffahrensführung the production in particular pharmaceutical, agriculturally or for the food production of important products or intermediate products. The well-known procedures of the immobilization of cells can be generally divided into physical, physical-chemical and chemical procedures, depending on whether the connection of the cells with the carrier e.g. mechanically, as with into a gel brought in cells, by Van of the Waals forces, via polar reciprocal effect or via kovalente connection takes place. Usually different synthetic or natural, organic or inorganic carriers, insoluble in water, are used which improve above all the hydrodynamic and Sedimentationsund thereby also the separate ion particularly clinging of the immobilized cells and contribute to the Stabilisierang of the desired enzyme activity. Different well-known kinds of the immobilization of cells, its advantages and sewing hurry as well as economic data hiezu are published in the form of overview articles (see for example Vandamme, chem. Ind. 24 (1976), 1072; Abbot, Advances Appl. Microbiol. (Hrsg. D. Perlman) 20, 203, Acad. Press. New York, San Francisco, London 1976; Jack and Zajic, Advances Biochem. Closely. 5 (1977), 126; Durand and Navarro, Proc. Biochem. 13, No. 9 (1978), 14 and Vojtisek et al., Biologick6 listy 44 (1979), 192). The physical immobilization of cells is for example in the CS-PS 113,908 (in agar) the ITPS 836,462 (with Cellulosela'iaeetatfasern), the US-PS 3,791,926 and the SU-PS 659,611 (installation of the cells into the network developing with the radical Copolymerisation of acrylamide with Methylen-bis) descriptive. The chemical immobilization of cells is article of numerous patent specifications, which for example to the kovalente connection of cells to different synthetic or natural polymers after preceding chemical Modif'tzierung and activation refer by different reagents. As carriers here numerous synthetic or natural organic materials and/or inert or chemically active polymers, for example on the basis of Methacrylaldehyd, serve Glycidylmethacrylat, Hydroxyalkylmethacrylaten, natural polymers, as for instance cellulose and their derivatives, collages, gel, inorganic materials, like glass, as well as for instance connections of titanium, zirconium, vanadium and such. Apart from the fact that preparations of in this way immobilized cells possess only a small specific activity and their particles are mechanically little verschleißfest, it is expensive hief'är used carriers of this type, whereby the price depends on the accesibility and the applied technology with the preceding chemical modification and activation by often very aggressive and toxic reagents; hiedurch the production and concomitantly the industrial utilization of immobilized cells are limited. A certain progress with the ZeUimmobilisierung with technical meaning comes out from the procedure of the CS-PS 197,101. The principle of this procedure exists in the connection of native production cells with Penicillinacylaseaktivität at cell carriers of different kinds of organism, whereby either whole uninjured and/or physically, chemically or biochemical cells or their not-soluble fragments chemically by kovalente connection using polyfunctional reagents, above all Glutaraldehyd treated, according to preceding physicochemical flocculation with flocculation means with connections with at least two primary and/or secondary amino groups in the molecule is preferably bound. With this kind of the immobilization of the cells lower production costs of the carrier obtained, since than carriers waste cells or mixtures of it or celluläre waste biomass of different fermentation processes disintegrated is used, their costs mostly very small are. A further, still more favourable kind of the chemical connection of Prodaktionszellen without use of carriers is in the CS-Urheberschein descriptive 203,607; this procedure is suitable universally for the mutual immobilization of cells without use of a carrier for prokaryotische and eukaryotische cells of microorganisms with different enzyme activity (see also the CS-Urheberschein 209,265). With this procedure very sturdy preparations are received mutually kovalent together from bound cells of different microorganisms, which exhibit the enzyme activity desired and exhibit integrals units of well sedimentierender particles. In principle hiebei native production cells with bifunctional interlacing Reagenfien, above all Glutaraldehyd, are chemically converted, whereby a kovalente connection of cell contents of the individual cells and a kovalente adjustment of the enzyme activity desired of the production cells as well as stability of these cells are obtained against natural or artificial Autolyse. In a further stage the interlaced cells are permeabilisiert by individual or combined effect of physical, physicochemical or chemical influences, whereby the No. 388933 Diffusionsbarfiere of the interlaced lines is eliminated by Ausschwemmen of macromolecular materials, which are components of the Oberflächenstruktttren of the lines and not with Glutaraldehyd reacted, for example by Lipiden. In the last Verfahrensstufe the interlaced and permeabilisierten cells in presence of a free Vernetzangsreagens, above all Glutaraldehyd, in the mixture with core-acting water-soluble substances with at least two primary and/or secondary amino groups in the molecule, above all Polyethylenimin and hexadecimal hexadecimaldiaminehexadecimal diamine, under conditions, which favour the gegenseiügen contact of the cells during the reaction, are bound for example for freezing, effect of centrifugal energy, of filtration printing etc., kovalent together. Due to the described process steps with the production of such immobilized cells it could be subordinated that the production is prepared already by biocatalysts on the basis of cell materials in sufficiently economical form. This is not valid however by no means generally and above all because with some enzymes available in the lines of production organisms with the simple penetration of aggressive, low-molecular cross linkage materials, as for example Glutaraldehyd enters, also with very low concentrations the intracellulären area rapidly an irreversible inactivating of the enzymes, whereby with some sensitive enzymes a substantial decrease of the enzymatic efficiency, probably by kovalente connections and thereby caused changes of the Raumstmktur of the active place of the enzymes, results which cannot be led back again into the original natural Konformation. This circumstance was determined particularly with some production cells with racemisierender or lytiseher activity. The Erf'mdtmg is according to the task at the basis a procedure for the production of biocatalysts on the basis of immobilized enzymatically active cell material to indicate, with which the disadvantages of the state of the art indicated above do not arise. The biocatalysts should possess thereby good sedimentation characteristics as well as a high specific activity and be accessible also in cases of highly sensitive enzymes with high immobilization yield. The task solved according to invention by immobilization of the enzymatically active cell material by Inkontaktbringen with a water-soluble, chemically reaküven polymer, which was received to one or more Dialdehyden by conversion of a wassedöslichen substance with at least two primary and/or secondary amino groups in the molecule with 0 to 60°C in an aqueous medium at a pH value from 4,0 to 12.0, with -30 to -50°C in a waßrigen medium and at a pH value from 5,0 to 9,0. From the DE-OS 29 15 135 a procedure is well-known that on the reaction of whole, enzyme-active cells or enzymes with Glutaraldehyd in presence of polyamine, in particular from branched Polyethylenimin is based: Intact cells + Polyethylenimin --> Flokulation --> Networking of developed flakes by free Glumraldehy& the principle is based thus on mutual kovalenter networking of the lines or enzymes by free Glutaraldehyd in presence of Korea-craving materials after preceding Flokulation by means of cation-active Flokulanten, which step with bifunctional Veruetzungsreagenzien into chemical reaction. In accordance with the procedure at-PS to 340,860 is based on the chemical reaction of whole or disintegrated cells, which are carriers of different enzyme activities, in presence of own or additional protein materials or polyamine and more differently inert fillers (felt, splinters, hair etc.) with Glutaraldehyd, under education of aggregates, which are posfformiert afterwards and possibly dried: Whole intact or disintegrated cells + protein materials or polyamine (possible in presence of fillers) --> Networking of the mixture with free Glutaraldehyd. The principle is based thus on a mutual kovalenten networking of whole or disintegrated cells in presence of protein materials or polyamine and fillers with free Glutaraldehyd, with possibly following post office formation of the particles and their drying process. In accordance with the procedure the US-PS to 4,212,943 is based on the preparation of cell aggregates of bacteria cells and its solidification by the contact of whole cells with (1) Glutaraldehyd or with Cyanurhalogeniden, e.g. Cyanurchlorid, and (2) with cation-active polymers, resulted from preceding reaction of Epihalohydrin with alkyl polyamine according to the following pattern: No. 388933 g 1 n - NH2 + CH2 - - CH2C1 R CH R2/g 1 N - R - NH - CH2 - CH - CH2CI R2) H g 1 -- “N - R - NH - CH2 - CH - CH2CI + HOC - (CH2) 3 - COH+ R2 OH (I) reaction product > bacterial aggregates intact bacteria cells the developed aggregates are dried after immobilization. The principle exists thus in mutual kovalenter networking of bacteria cells by free Glutaraldehyd in presence of the product of a reaction of epichlorohydrin with Alkylpelyamin. Those managing discussed procedures differ in principle from the erfmdungsgemäßen procedure. This concerns the production of biocatalysts by immobilization of enzymatically active cell material out whole, intact native or if necessary before permeabilisierten cells or cell fragments and of them subcellulären particles and/or - mixtures of whole, native cells with their cell fragments, subcellulären particles and all set free cell contents and/or - whole, individually interlaced and permeabilisierten cells. These cells developed brought in contact with a chemically reactive polymer (RLP), soluble in the water, by chemical reaction of bifunktioneUer aldehydes of the dicarbonic acids, in particular the Glutaraldehyds, with water-soluble materials, which contain at least 2 primary or secondary Aminogrnppen, in particular with Polyethylenimin, hexadecimal hexadecimaldiaminehexadecimal diamine, Lysin or Polylysin. Favourable further educations of the procedure according to invention are the subject of the Unteransprüche 2 substances with at least two primary and/or secondary amino groups, water-soluble to aptitudes, in the molecule are for example hexadecimal hexadecimaldiaminehexadecimal diamine, Lysin and Polylysin and preferably Polyethylenimine. Preferential Dialdehyd is Glutamldehyd. Erfindunsgsgemäß the manufactured biocatalysts contained as cell material prokaryotische or eukaryotisehe cells of Organsimen, in particular of grampositiven, gramnegativen and gramlabilen bacteria, acid-resistant bacteria, actinomycetes, yeasts and other microscopic mushrooms as well as higher, above all parasitic mushrooms and plant cells, if necessary also their fragments and subcelluläre particles, which carry Enzymaküvität. These cell materials and from them manufactured biocatalysts contain enzymes, in particular hydrolase, Isomerasen, Lyasen, Decarboxylasen, Oxidoreductasen and other enzymes and/or parts enzyme sequences of biochemical reaction sequences, in particular the degradativen Netabolismus, the Glycolyse, of Horrnonbiotransformationen as well as enzymes of alkaloid production, entire of enzyme sequences or, in particular from Solanum alkaloids and Phytosterinen as well as ergot alkaloids. It is favourable according to invention to use for the production of the water-soluble polymer as well as for the possible preceding flocculation of the cell material an aqueous solution of a Polyethylenimins with a molecule mass within the range of 100,000 to 800,000. The conversion of the cell material with the polymer is preferably accomplished at a temperature from 0 to 45°C, a relative centrifugal acceleration from 1 to 50,000 and/or a filtration printing from 0 to 000 kPa under leaving untouched, slow agitating or agitating with interruptions and the leaving of the reaction mixture untouched. The Permeabilisierung of the native cells before the immobilization or the received cell aggregates after the immobilization can through agitating the appropriate suspension of the cell material in an aqueous medium at temperatures from 0 to 70° (2 and a pH value from 4,0 to 9.0 in presence of a Tensids and/or of organic solvents non-mixable mixable with water and/or to be accomplished, in particular with acetone, Ether, isopropanol, Petrolether, butyl acetate, chloroform, Dioxan, dimethylformamide or Dimethylsulfoxid, whereby the ion strength of the suspension is changed at the same time or afterwards by addition by salts of strong acids and/or alkalis. The particles of the immobilized cells become if necessary by partial Dehydratation by effect of organic L0sungsmittel, preferably acetone, as well as if necessary with solutions of No. 388933 adhesives in organic solvents or their mixtures with water at temperatures from -25 to “+20°C further mechanically verfesägt; furthermore the developed particles can be sucked off and be reproduced in a dry or damp medium partly dried as well as if necessary in an appropriate way. According to invention obtained the advantages are substantially in it that with the help of the chemically reactive, water-soluble polymer biocatalysts on the basis of immobilized cells with high specific activity, good sedimentation characteristics and high immobilization yield are accessible, also in cases of hochempf'mdlicher enzymes, in which in accordance with the CS-Urheberscheinen 1 97 101, 2 03 607 and 2 09 265 will not proceed can, since contrary to these well-known procedures, with those free, low-molecular Vemetznngsmittel is used, which is reakUve polymer in the erf'mdungsgemäßen case in water lösäch, however already a so high molecule mass possesses that it cannot penetderen no more into the cells, and a kovalente connection between the ZeUenoberfläche and reactive groups of aldehydes of the activated reakäven Polymer under immobilization one obtains. The actual mechanism of the education chemically more reactively and in water of soluble polymere ones, for example using Polyethylenimin and Dialdehyden, like in particular Glntaraldehyd, is based to I5 probably on the internal networking of the Polyethylenimins under preferential education of colored Schitr bases by reaction of the groups of aldehydes of the Glutaraldehyds with primary or secondary amino groups of the Polyethylenimins (C=N-Bindungen), which to a rise of the Moleküimasse and to the simultaneous chemical Aküvierung of some primary or secondary amino groups leads, which are present in branched and probably finalconstant chains of the Polyethylenimins, furthermore by chain transmission on reactive groups of aldehydes, whereby the developing vemetzte, chemically reactive polymer in an aqueous remains solution-solved, and the resulüerende solution of the reactive polymer a clear, transparent yellow-brown to red-brown Liquid represents. The procedure according to invention covers two in principle process steps: In a first step the chemically reactive, water-soluble polymer will be used preferably by conversion of commercial Flocknngsmittel with a content of a Frakäon of a Polyethylenimins, like it for the waste water purification, with a Dialdehyd as cross linkage material, in particular Glutaraldehyd, in an aqueous medium and preferably under agitating the reaction mixture manufactured. The speed of the polyreaction can e.g. on the basis the concentration increase of the colored Schiff bases in the visible spectral area, for example with 550 Nm, by which change of the absorption is determined, whereby the Konzentraüon is dependent on the relationship of the two reaction components, thus the cross linkage material and the connection converted thereby, as well as the reaction duration and the reaction temperature particularly. The reaction can here kinetic by a time law of first order bescluäeben to become. Interfered in the second Reakfionssmfe into the partial or quantitatively converted solution of the reactive polymer native, fresh, before mikrobielle or vegetable toes with the desired enzyme activity, separated from the cultivation medium, and/or interlaced and permeabilisierte cells in cases, if the sensitivity of the enzyme concerned makes preceding application for a free solution possible of the cross linkage material, and if necessary mixtures of whole naive cells and disintegrated cells in form of a suspension with the ZeUdesintegrafionsfragmenten, whereby size, form, kind, porosity and specific activity of the immobilized cell materials by the applied lmmobilisafionsverfahren, in particular freezing, leaving, weak agitating untouched, effect of a filtration printing, a centrifugal field, pressing the suspension or the developed particles out by suitable Eiurichtungen and following partial Drying process of the particles in a dry or damp environment, to be adjusted know. Furthermore the procedure according to invention covers also the Permeabilisation of the cells before the immobilization and/or the developed cell aggregates after the immobilization as well as if necessary attached further process steps, in particular in the cases, in which as raw material whole native cells were used, whereby the received immobilized particles can be submitted if necessary for the increase of their mechanical stability and firmness of a subsequent treatment, in particular by partial Dehydrataaon of the particles by treatment with acetone or other organic solvents, which forms a protecting micro layer of an water-insoluble film on the surface of the particles after partial drying up; hiebei the subsequent treatment conditions are individually selected regarding the limitation of the enzymatic reaction rate by diffusion. For the erfmdungsgemäßen production of the biocatalysts cannot in principle only be used different kinds and trunks of prokaryotischer and eukaryotischer mikrobieller cells with different Enzymaküvität, but also plant cells, mikrobielle like also actual vegetable cells, without consideration for whether the enzymes with the desired enzyme activity are located in the periplasmatischen or intracellulären area (in the Cytoplasma of the cell). The invention concept is accordingly in very broad framework applicable, as from the Ansführungsbeispielen follows, whereby the kind of the enzyme and/or the type of the enzyme-catalyzed biochemical reaction desired is crucial not in principle. For a given type of prokaryotischer or eukaryotischer cells it is regarding the localization of the enzyme desired in the cell and the quality of the enzyme and/or the type of the enzyme-catalyzed biochemical reaction and the well-known or No. 388933 presupposed chemical composition of the cell surface (Peptidoglucan, Lipoprotein, Lipopolysaccharid, Chitin, Chitosan and such) necessarily, the procedure of the immobilization, for example under freezing, leaving, agitating untouched etc., to select and above all the procedure with the Permeabilisaüon of the cells before and/or after their education in an appropriate way particularly in particular, if as Ansgangsmaterial for the immobilization freshness, intact, native living cells to be used. Furthermore the actual Immobilisiernng according to invention is also regarding the presupposed frequency and accesibility of reacting groups, which are components of the cell surface and also by kind and physiological condition of the immobilized cell population are certain to select. In cases, in which or presupposed is that with the assigned cells the frequency and accesibility of the reacting groups are only small on the ZeUoberfläche, in particular with vegetable cells, can the erfmdungsgemäße procedure admits with a preceding Flokkulation of the native cell suspension with such Flockangsmitteln is favourably combined, the connections with at least two primary and/or secondary amino groups contain; in this way physicochemically formed aggregates are interfered before either after sucking off or directly into the solution of the reactive polymer, with which on the one hand the mutual contact of the cells is facilitated with one another and on the other hand the cell surface is enriched on into the reaction entering groups. For the production according to invention of the biocatalysts production cells can be used, be contained the different enzymes, different kinds and trunks of bacteria, actinomycete, yeasts, Fungi imperfecti, higher parasitischen mushrooms and plant cells. It is favourable furthermore to use for the Immobilisiernng such cells those by breeding, selection, Ronzentrierungsverfahren or genetic manipulation won mutante organisms represents, since then the won immobilized preparations exhibit a high specific activity. The size according to invention of the particles from bound cells, received in the procedure, was determined light-microscopically with a special measuring eyepiece. Furthermore some preparations were scanning electron microscope examined. The sedimentation characteristics were determined in the way that 2.5 g wet preparation mass in altogether 25 were suspended ml entmineralisiertem water in a Meßzylinder and the time necessary for the quantitative sedimentation of the particles were determined. Furthermore for the Ermitflung of the particle size metallic Prüfsiebe were consulted for the Siebanalyse, whereby the bound cells were fractionated depending upon size with three sets of these Prüfsiebe with mesh sizes of 0,03 to 2.00 mm. The enzymatic activity of the immobilized materials was determined under agitating and Temperiernng of a defined quantity of the particles of the bound cells in a substrate solution within the range of kinetics of zeroth order of the Enzymreaküon, whereby the enzyme activity is indicated in the examples in form of the specific activity as quantity of IJJnol product (e) per mg and/or g wet preparation mass, if nothing else is mentioned. The preservation of the entire Enyzmreaktionssequenz in the immobilized cells became manometrisch on the basis the total production of (202, which was formed protecting for a determined time from Saecharose, determined. In the case of the Produküon of different alkaloids, in particular Solanum alkaloids and Phytosterinen, these materials were determined by ii-PLC chromatography. The received particles according to invention manufactured of the biocatalysts from immobilized cells can be preferably reproduced after if necessary effected mechanical Veffestigung by partial Dehydratation by Einwkkung of organic solvents, by acetone, if necessary with solutions of commercial adhesives in organic RST singing means, after sucking off and partial drying process under dry or damp conditions in an appropriate way, whereby size, form, kind, porosity, specific activity and sedimentation characteristics of the immobilized materials to be adjusted to be able. In the following remark examples the commercial flocculation means are used as substances with at least two primary and/or secondary amino groups in the molecule, which contain Polyethylenimine with molecule masses from 200,000 to 300 1300 in a concentration of approximately 30 mass %. The following remark examples describe the Erf'mdung. Example 1: Became 100 each ml a solution of technical Polyethylenimin in entmineralisiertem water with a concentration of 1,0% (M/V) and/or 2.0% (M/V) manufactured. The solutions were recast in 500-miSiedekolben, which was brought on a rotation mechanical shaker (260 rpm). Into these solutions, whose pH amounted to 6.1, a 25%ige aqueous solution was admitted by the Glutaraldehyd in the way that its concentration in the reaction mixture in the first case 0.5 VOL. - % and in the second case 1.0 VOL. - amounted to %. The pistons with the reaction mixtures were covered with aluminum foil; after switching on of the mechanical shaker on in given time intervals the polymerization speed was pursued speklIophotometdsch with 550 Nm. The reaction was accomplished under continuous agitating at a temperature of 20°C. The absorption values of the individual, time-dependently pulled samples were measured against entmineralisiertes water. The results, which show the concentration rise of the Schiff bases for both reaction mixtures, are specified in table 1 No. 388933 table 1 reaction mixture 1.0% (M/V) technical Polyethylenimin 2.0% (M/V) technical Polyethylenimin time (h) + 0.5% (VN) Ghtaraldehyd + 1.0% (V/V) 0,0.5,0.8 0.15 0.25 0.81 0.30 0.36 0.75 1.0 0.54 1.05 (*) 2.0 0.60 1.20 3.0 0.64 1.26 4.0 0.68 1.28 5.0 0.70 (*) 1.32 6.0 0.72 1.36 7.0 0.75 1.40 24.0 0.90 1.60 Glutaraldehyd (*) these absorption values after dilution of the samples with enlmineralisiertem water, steep thus absolute absorption values were computed after conversion. After 24 h reaction duration were present red-brown colored solutions with a pH value of 4,9. Into in the way indicated above the manufactured converted solutions of the reactive polymer under intensive agitating in each case 25 g (damp mass) were interfered whole intact bacteria cells by Alcaligenes of metalcaligenes in form of a not washed wet cell paste with Aspartatammoniak Lyaseaktivität, which was won after cultivation by centrifugation. The specific activity of the cells amounted to 550 larnol L-Asparaginsäure/min. g, related to the damp mass, when 37°C, pH 8.5 and using a 1,35-M-Lösung von Ammoniumfumarat as substrate. After interfering the cells into each of the reaction mixtures the homogeneous suspensions in two Ahminiumschalen with a diameter of 20 were recast em, whereby the Fiillhöhe amounted to about 1.5 em, and afterwards 4 h with -20°C in a Tiefkühlbox stored thereafter frozen bowl contents with approximately 100 were poured over ml entmineralisiertem water, on which the bowls thaw 1 h out at ambient temperature slowly were left. Subsequently, the received aggregates in Glasget'äße recast, which 11 entmineralisiertes water contained, after slow mixing and quantitative sedimentation after leaving untouched were poured off the washing water and the received product still three times with 1 1 tap water was decanted. The received particles were then abgenutscht and won on a frit with textile edition in the vacuum well. And from the second Reaktionsgemiseh 18.2 g immobilized cells (in each case damp mass) were received from the first reaction mixture to 16.0 g. The biochemical and further characterisation of the two immobilized materials was described accomplished above as; the received results are summarized in table 2: Table 2 Ro lJv polymer sImz. Aküvität Oamol L-Asparaginsiture/min.g) Teilchengrö nbereich (lam) microscopic picture Sedimentaüon 1 2 420,500 100-450 300-600 limited panels limited panels quantitatively in 10 min quantitatively in 5 min example 2: . A solution of a reactive polymer was manufactured as in example 1 (initial concentrations 2.0% (M/V) technical Polyethylenimin and 1.0% (V/V) Ghtaraldehyd). In 100 ml the solution of the reactive polymer 25 g bacteria cells were interfered intensively as in example 1: subsequently, as in example 1 one proceeded. 17.2 g (damp mass) well sucked off aggregates with a specific activity were won by 512 lamol L-Asparaginsäure/min. g. The received material was suspended in 50 ml a 5% password of synthetic adhesive in acetone, which was cooled down before auf-20°C: after 3 min Riihren with Ranmtemperatur was sucked off sharply the material in the No. 388933 way in the vacuum, indicated above, and continued to suck off still about 15 min on the frit, in order to obtain a partial Trocknnng of the adhesive on the surface of the individual particles. Afterwards 10.5 g material were weighed out and suspended in 100 ml a 1,35-M-Lösung von Ammoniumfumarat with pH 8.5 and stored over night at ambient temperature with +8°C. After renewed Absangen in the vacuum the material on the frit was washed with 1 1 water and weighed after good sucking off (13.0 g). The specific activity of the material amounted to 180 gmol L-Asparaginsäure/min. g (Feuchtrnasse). The material consisted of firm, rough, limited panels with a Teilchengr6ße within the range of 400 to 600 lma. After 2 min leaving untouched was present quantitaüve sedimentation. Example 3: It a solution of a reaküven polymer as manufactured in example 1 and 2 with the difference that under otherwise identical conditions the reaction duration amounted to 3 h. In 100 ml this solution of the rh-active polymer 25 g bacteria cells were interfered as in example 1 nnd 2; subsequently, to the production of the immobilized cells as muddled in example 2 with the difference that before the treatment the material with the solution of the adhesive in acetone the aggregates were permeabilisiert by 3 h agitating on a rotation mechanical shaker with 260 rpm with 30°C in 100 ml 1.0 M an aqueous solution by ammonium sulphate with pH 8.5 and a content of 0,1% of a Tensids. Subsequently, the material was washed in the way in the vacuum, indicated above, well sucked off, with 1 1 water, sucked off, weighed again (16.0 g) and then further-treated as in example 2. 10 g immobilized cells (damp mass) with a specific activity were won by 250 lamol LAsparaginsäure/min. g (damp mass); the material consisted of firm, rough, limited panels with a middle particle size from 300 to 550 lam; by 3 min leaving untouched entered qnantitative sedimentation. Example 4:300 g of a fresh wet paste separated from native whole bacteria cells from Escheriehia coli, those after cultivation by centrifugation were and a specific activity at Penicillinacylase of 8,0 I.tmol 6-APK/h. mg (damp mass) 42°C, pH 7.6 substrate potassium salt of BenzylpeniciUin) exhibit, became in 1 1 of a solution of a reaküven polymer, which by conversion 2% igen (M/V) solution of technical Polyethylenimin and a one percent (V/V) password Glutaraldehyd with 30°C during one reaction duration manufactured by 24 h after the Veffahrensweise of example 1 was suspended, in form of a homogeneous Snspension by intensive agitating with a steel propeller mixer. The suspension was divided ansehliegrend in four same Volumteile (to 320 ml); each part was brought separately into Igelitsäcke, which were umgefalzt several times and locked with metal clips; the bags were stored in horizontal situation in a Tiefkühlbox with -20 to -25°C about 5 h, whereby the layer thickness of the reaction mixture amounted to with the horizontal storage of the bags about 1.5 to 2 cm. After this time the bags were taken as the Tiefkühlbox; frozen contents were mechanically cut up in the bags; the bags were afterwards cut and their contents were brought into 10 of 1 submitted entmineralisiertes, 25°C warm water in a Glasgef'äß. The material was then thawed during 1 to 2 h by mild, interrupted agitating out, after quantitative Sedimentaüon of the formed particles by the washing water abdekantiert and afterwards still three times with 5 1 tap water decanted. Subsequently, the aggregates on a Nutsche were sucked off sharply with textile coating in the vacuum, on that Nutsche still with 5 1 tap water washed and afterwards in form of the wet filter cake again well abgesangt. 215 g of the wet preparation mass of the well abgesangten material became then under agitating in 500 ml one before on -15°C of cooled down acetone water mixture (1: 1) suspended and 3 min with Ranmtemperatur in diluted acetone intensively through-mixed; afterwards the material was sucked off sharply in the vacuum, through-sucked still to 5 to min on the Nutsche and washed afterwards with approximately 5 1 tap water, abgesangt again well, suspended in 1 10,05-M-Phosphatpuffer with pH 7.6 and over night with +8°C pour to let. Altogether 180 g became immobilized cells (Fenchtmasse) with a specific activity at Penicillinacylase of 6,5 tamol 6-APK/h. mg (damp mass) won; the material existed to the limited Plattchen with a particle size within the range of 150 to 450 lam; by 5 min leaving untouched was obtained quantitative sedimentation. Example 5:250 g (damp mass) interlaced and permeabilisierte bacteria cells of Escheriehia coli with Penieillinacylaseaktivität (specific activity 7.0 l.tmol 6-APK/h. mg ('damp mass), which in accordance with the procedure of the CS-Urheberscheins 2 03 607 interlaced and it had been permeabilisiert had been interfered in 1 1 of a password of a reactive polymer, manufactured as in example the 1 was with the difference that the reaction duration amounted to 5 h. After mixing the cells in the Lösnng of the reactive polymer to a homogeneous suspension the immobilization of the cells was made in accordance with example 4 including the treatment of the material with the acetone water mixture. Altogether 166 g (Fenchtmasse) were received to immobilized cells with Penicillinacylaseaktivität, their specific activity 6.0 lmaol 6-APK/h. mg (damp mass) amounted to; the material consisted of limited brown-black panels with a particle size within the range of 180 to 400 lam; by 3 min leaving untouched was obtained quantitative sedimentation. No. 388933 example 6:40,0 g (damp mass) fresh native cells of Escherichia coli with Penicillinacylaseaküvität in accordance with example 4 were suspended homogeneous in 150 ml one as in example 4 manufactured solution of a RH, active polymer; the mixture was distributed on 10-ml-Polyethylenkfivetten. The formation of aggregate particles of the immobilized cells by the effect of different relative centrifugal accelerations were affected. The reaction was accomplished 3 h with 20°C. After the reaction the preparations were decanted twice treated with water, over textile material in the vacuum sucked off and as in example 4 with an acetone water mixture and over night pour left. Subsequently, the preparations were sucked off, weighed out again in the vacuum and continued to characterize. The received results are summarized in table 3. Table 3 relative Zenlrifugalbeschleunigung (g) 600 1100 4 500 10 200 middle particle size (mm) 0.2-0.45 0.4 - 0.85 0.55 - 1.2,0.8 - 2.0 sedimentation speed of the particles (min/I. kg) specific Aküvität (l.tmol 6-APK/h. mg) (damp mass) 7.0,6.5 5 3.1 microscopic picture unlimited forms with irregular edges macroscopic picture brown amorphous particles note: The evaluation of the immobilized preparations took place as above besehrieben. Example 7:28 g (damp mass) of a fresh paste of native lines of Escherichia coli, which contained the enzyme Galactosidase, in 100 ml a solution of a reactive polymer it was suspended intensively which had been received by 24 h conversion in accordance with example 1, however with the difference that the initial concentration of the two Reaküonskomponenten technical Polyethylenimin and/or 2.8% (V/V) Glutaraldehyd amounted to. The specific activity of the fresh naäven cells in the paste amounted to 0.42 I.tmol glucose + Galactose/min. g (damp mass) of the native cells (37°C, pH 7.0, solution of lactose as Substra0. The homogeneous cell suspension was sucked off by 2h leaving untouched at ambient temperature converted to it the developed spongelike precipitate of the cell aggregates in the way in the vacuum, described in the above examples, and the received mass was brought in form of a wet cake into a fabric bag; the opening of the bag was umgefalzt and locked with metal clips; the bag was brought in for a Filtraüonsdruck in horizontal situation between metal plates and suspended with a hydraulic press at ambient temperature 2 h long of 1,25. 104 kPa. Afterwards the dark, mechanically by breaking to smaller pieces, was cut firm mass up in form of a plate which were registered in 1130 ml in a household mixer submitted water and disintegrated in it when the lowest number of revolutions and interrupted switching on on to smaller particles. After disintegration and Homogenisation the material was well sucked off, weighed three times with 0,5 1 water decanted, in the vacuum (16.2 g) and brought into 100 ml a 1-M-NaCI-Lösung, which 0.2% (V/V) Tensid and 1% (V/V) Dimethylsulfonid contained. The suspension was kept at a moderate temperature on 40°C and agitated continuously 3 h at this temperature. After the Permeabilisation the particles were sucked off three times with 1 1 tap water dekanüert, in the way indicated above registered in the vacuum well, then in 0, l-M-Phosphatpuffer pH 7.0 and over night pour left. After sucking off and washing the immobilized cells altogether 30.2 g (damp mass) were received irregular, whose specific activity amounted to 0.12 I.tmol glucose + Galactose/min. g (damp mass to dark, amorphous particles in form very fast sedimentierender lump,); the particle size lay within the range of 0,5 to 2.6 mm. Example 8:30 g (damp mass) native whole lines of Escherichia coli with l - Galactosi daseaktivität as in example 7 into 100 ml 0,5-M-NaC1-Lösung were brought, which contained 0.5% Tensid; the suspension was thoroughly homogenized by intensive agitating and recast afterwards into a 500-ml-Siedekolben, which was covered with aluminum foil and set on a rotation mechanical shaker with 260 rpm. The suspension of the native lines was permeabilisiert 20 min under continuous agitating at a temperature of 30°C No. 388933. The cells were centrifuged afterwards with -20,000 10 min; the projection was together-poured; the sediment of the cell paste was weighed. 26 g (damp mass) of the cells treated in the indicated kind were suspended in 100 ml a solution of a reactive polymer, which had been manufactured as in example 2, to a homogeneous suspension; the immobilization of the cells by freezing of the Reaküonsgemischs as well as treatment of the developed particles after the immobilization as made in example 2 with the difference that 17 g (damp mass) of the developed particles in 50 ml auf-20° C cooled down pure acetone were suspended before, and the treatment with acetone when intensive agitating 3 min was long made, on which the material fast and on a frit in the vacuum sucked off, washed with water and over night in a medium of 0,1-M-Phosphatpuffer pH 7.0 with +8° C poured sharply was left. Altogether 12.6 g (damp mass) of the immobilized cells with a specific activity at BGalactosidase from 0,38 gmol + Galactose/min. g (damp mass) were received to glucose; the particle size amounted to 400 lam. The material consisted of panels with irregular edges; by 5 min leaving untouched was obtained quantitative sedimentation. Example 9:2,5 kg (damp mass) fresh native cells of Bacillus megatherium, which had been harvested before completion of the exponential growth phase and a proteolytic activity of 38 Azocaseineinheiten/g (damp mass) (37°C, pH 7.5, substrate Azoeasein) exhibited, were suspended in 10 1 entmineralisiertem water; the suspension was homogenized by intensive agitating and cooled down on +5°C. The suspension was disintegrated afterwards by three-way passage by a meehanischen slot the integrator with a pressure by 253 bar. The suspension was cooled constantly in such a way between the individual Desintegraüonsschritten that a maximum temperature of the disintegrated mixture of 35°C was not exceeded. To 1 1 of the disintegrated suspension of the native cells, whose pH value with 20%iger NaOI I solution under continuous agitating on 7,5 was regulated, technical Polyethylenimin was admitted as flocculation means in such a quantity that the concentration in the disintegrated suspension 0.25 VOL. - amounted to %. The suspension was calmly left untouched after thorough mixing at ambient temperature about 1 h, until quantitative flocculation of the disintegrated cell material was determined. Subsequently, to 1 1 of the suspension 21 of a solution of a reactive polymer it was added which had been manufactured by 24 h conversion after the procedure by example 1 with the difference that the initial concentration of the two reaction components 4% (M/V) technical Polyethylenimin and 2% (V/V) Glutaraldehyd amounted to. Interfering the 2-1-Lösung of the reactive polymer was accomplished by slow agitating with the hand with a staff from stainless steel in the way that the before flokkulierten particles were not damaged. After 2 h leaving untouched was slowly through-mixed those strongly viscose rayon ausgeflockte and partly abreacted suspension and distributed on 10 polyethylene bags of approximately 0.3 1 contents; subsequently, as muddled in example 4 further with the difference that the immobillsierten particles were before treated according to the immobilization with pure, acetone 3 min under intensive agitating, cooled down on -20° C, on which they were sucked off sharply in the vacuum, several times with water were decanted and brought into 11 O, 1-MPhosphatpuffer pH 7.5, in which it over night with +8° C pour were left. Altogether by the procedure indicated above 1.28 kg immobilized particles (damp mass) were received by the gradual treatment of the output suspension, whereby the specific activity of the material amounted to 3.62 Azocaseineinheiten/g (damp mass); the particle size lay within the range of 0,4 to 2.0 mm; by 2 min leaving untouched was obtained quantitative sedimentation. Example 10: In 100 ml 0.05 M an aqueous NaCI solution, whose pH value with 20%iger NaOI I solution on 7,0 was regulated, were suspended 50 g (damp mass) fresh, whole native cells by Bacillus megatherium with proteolytic activity as in example 9. After the homogenization of the suspension the pi-IWert was regulated again in the way indicated above to the value 7.0; subsequently, lyophilisiertes EiLysozym was admitted in the way that its concentration in the suspension 1 (30 I.tm/100 ml amounted to; after min leaving untouched was stopped the pH value of the suspension carefully with the NaOI I solution under agitating to 8,6 and the suspension some min to 50° C considered, until due to the enzymatic Lyse of the cell walls the viscosity of the suspension suddenly changed. Subsequently, to the suspension without preceding Flokkulation 100 ml in accordance with example 9 it was admitted to the solution of the reactive polymer with a concentration of the Reaktionskompenenten on which the suspension was mixed intensively. Afterwards for immobilization including the treatment of the particles with acetone in accordance with lmmobilisierung in accordance with example the 8 (freezing of the reaction mixture) one proceeded. 30 g (damp mass) were won immobilized particles, whose specific activity amounted to 2.4 Azocaseineinheiten/g (damp mass); the particle size lay within the range of 0,2 to 1.0 mm 3 min. Leave untouched led to quantitative sedimentation. Example 11:30 g (damp mass) of a fresh native paste of cells of the yeast Kluyveromyces fragilis, which the enzyme B-Galaetosidase with a specific activity of 0,017 gmol glucose + Galactose/min. g (damp mass) (37 C, pH 6.0, substrate lactose) contained, in 100 ml O, 1-M-Phosphatpuffer pH 7.0 No. 388933 was suspended, the 0.19% Tensid and 1% Dimethylsulfonid contained after warming up auf40° C the suspension at this temperature 30 min was continuously agitated. Afterwards the permeabilisierten cells were centrifuged (50 g, 10 min); after pouring off the projection the sediment of the cell paste was weighed. g (damp mass) in this way of the permeabilisierten cells were immobilized and further-treated as in example 8 with the difference that the particles were treated and poured according to the Immobifisierung with a one percent password of synthetic adhesive in acetone under otherwise identical conditions as in example 8. 15 g (damp mass) were won immobilized cells with a specific activity of 0,02 grnol glucose + Galactose/min. mg (damp mass) of the particles, the particle size lay within the range of 0,2 to 1.5 mm; by 2 min leaving untouched the cotton wool-like aggregates sedimentierten qnantitativ to a relatively extensive sediment. Example 12:25 g (Feuchlrnasse) blows whole cells of the yeast Cryptococcus laurentii with L-alpha-Amino - aminocaprolactamhydrolaseaktivität with a specific activity of 5,9 tmol L-Lysin/h. mg (Feuehtmasse) (37 C, pH 7.5, substrate aqueous L-alpha-Amino - caprolactam) under intensive agitating in 100 ml a solution of a reactive polymer, which was manufactured as in example 2, were suspended; after slow agitating during 1 h those was solidified strongly viscose rayon cotton wool-like suspension as in example 2 by chilling including treatment of the aggregates lmmobilisierung by treatment with an adhesive loosened in acetone. The received sucked off aggregates were let pour over night in phosphate buffer pH 7.0 with +8° C. 15 g (damp mass) became immobilized cells with a specific activity of 3,2 tmol LLysin/h. mg (damp mass) with a particle size won within the range of 0,125 to 1.5 mm; by 2 min leaving untouched was obtained quantitative sedimentation. Macroscopically the material had amorphous, cotton wool-like appearance; the microscopic investigation resulted in irregularly formed particles with irregular Rändem. Example 13:30 g (damp mass) of a paste from fresh native cells of Nycobacterium frames, which the enzyme L-Asparaginsäure-decarboxylase with a specific activity of 7,1 E/g (damp mass) contained (1 unit E of the enzyme effectiveness corresponds to the enzyme quantity, which sets IOO free gl CO2 with 30° C and pH 5.5 during min from L-Asparaginsäure), in 100 ml a solution of a reactive polymer as in example 2 to a homogeneous suspension were suspended; subsequently, by freezing of the reaction mixture including Dekantation, washing and sucking off as in example 2 one continued to proceed. 19.6 g (damp mass) immobilized cells were won. This particle quantity was suspended in 100 ml l-m-NaCI-solution with pH 6.5, in which 0.5% Tensid was solved. Into this suspension chloroform became a concentration of 5 VOL. - % admitted: the suspension was then warmed up under agitating to 35° C and agitated intensively at this temperature 1 h. Subsequently, the suspension with 1 1 water diluted and three times with 1 1 water decants was sucked off the permeabilisierten particles in the way in the vacuum, described in the above examples, suspended before after sucking off in 50 ml on -25° C cooled down acetone and agitated intensively 3 min at ambient temperature. Afterwards the particles were washed again sucked off, on the frit thoroughly with water, suspended in ml 0,05-M-Acetatpuffer with pH 6.0 and left untouched for swelling over night with +8° C. 14.2 g (damp mass) immobilized cells with a specific activity were won by 4,0 E/g (damp mass). The particle size lay within the range of 75 to 800 I.tm; when macroscopic evaluation the particles formed grey-yellow cotton wool-like things with badly wettable surface. The immobilized cells showed a bad spontaneous sedimentation, i.e. held themselves in the top of the liquid in the lift; they could be however easily filtered and sucked off. Example 14:30 g (damp mass) of fresh naüver cells of Bacteraum cadaveris, which the enzyme LLysindecarboxylase with a specific activity of 16,4 E/g (damp mass) contained (1 unit E of the enzyme activity corresponds to that enzyme quantity, which sets 100 Ixl free C02 with 30° C and pH 5.5 from L-Lysin), in IOO-ml-l_.6sung of a reactive polymer as in example 2 to a homogeneous suspension suspended thereafter by freezing including Dekantation, washing and sucking off as in example 2 were continued to proceed. 24 g (Fenchtmasse) were won immobilized cells. This quantity of the sucked off particles was suspended in 100 ml l-m-NaCI-solution with pH 6.5, which contained 0.1% Tensid; the suspension was agitated continuously with 37° c1 h. The further treatment of the immobilized and permeabilisierten cells happened as in example 13. 19.1 g (damp mass) immobilized cells with a specific activity were won by 11,8 E/g (damp mass) with a particle size within the range of 180 to 600 I.tm; the particles appeared macroscopic as amorphous, brown particles; the microscopic investigation resulted in particles in form of limited panels from 3 min leaving untouched quantitative sedimentation was obtained. Example 15:20 g (damp mass) of a paste from fresh naüven cells of the yeast Saccharomyces cerevisiae, those the enzyme Invertase with a specific activity of 148 E] g (damp mass) (30° (2, pH 4.75, substrate saccharose) contained, in 1OO-ml-Lösung of a reactive polymer as in example 2 to a No. 388933 homogeneous suspension were suspended; the further immobilization with freezing including the further process steps happened as in example 2. the treatment of the cells with acetone as in example 8 was accomplished. I2,1 g (damp mass) were won immobilized cells with a specific Aküvität by 90 E/g (damp mass) with a particle size within the range of 0,32 to 2.0 mm; the particles formed macroscopically hellbranne to beige amorphous particles; the microscopic investigation resulted in unlimited formations of particles with urtregelmäßiger morphology and torn edges; by 2 min leaving untouched was obtained quanütative sedimentation. Example 16:1 1 fertile soil, which had been cultivated submers and a fresh culture contained Saceharomyces of the yeast coreanus, was centrifuged (relative Zentrifngalbeschleunigung 3000, 10 min); after pouring off the projection (Nahrboden after the fermentation, for which one had kept) 28 g (damp mass) were won fresh native cells. This quantity of the fresh yeasts in form of the cell paste was suspended in 100 ml a solution of a reactive polymer, which had been manufactured in accordance with example 2; , after thorough homogenization of the suspension by intensive agitating the reaction mixture was put on on laboratory vibration equipment and 1 h at ambient temperature with 50 oscillations/min was vibrated. Afterwards mixing was stopped and the suspension 3 h at the indicated temperature in peace was left. That became subsequently, strongly viscose rayon, spongelike mash from the produced. Aggregates in 500-ml-Polyethylenbehälter recast and in the way indicated above centrifuges; the Uberstand was poured off and the sediment in entmineralisiertem water and decanted three times with 250 was suspended ml water under mild agitating. After the Dekantation and quanütativen sedimentation the material in the vacuum was sucked off, washed and weighed with approximately 100 ml water (14 g). Subsequently, the material in 25 was suspended before ml on -25° C cooled down acetone and agitated intensively 2 min. Afterwards the material on the frit was sucked off sharply and weighed in the vacuum (9 g). The won damp mass from immobilized cells was snspendiert in, the centrifuged projection liquid indicated above (fertile soil for the yeast fermentation) and some hours at ambient temperature pour calmly. The material was well sucked off afterwards again in vacuum. 100 mg (damp mass) of the particles into a being castle container one weighed; afterwards 2 was admitted ml centrifuged, clear fermentation liquid with pH 4.6; into the arm of the being castle container 0.5 ml 12.5% ige saccharose solution were in-pipetted; to one the ReferenzgePäße the native, not-immobilized cells (100 ml the native damp paste) were given and shifted with 2 ml to centrifuged fermentation liquid; into the second reference container the own projection (without cells) was admitted and into the arms the saccharose solution. After using the manometers the being castle container 15 min was vibrated with 30° C. Subsequently, the manometers were aired out; after pouring over the saccharose solution to the arms began the actual measurement of the CO2-Entwicklnng. During the first check measurement (not-immobilized separate naive cells) 3064 tl CO2 was developed; during the second check measurement (projection without cells) no CO2-Entwicklung arose; with the third Konlrollmessung (immobilized cells with same concentration at damp mass as during the first check measurement) 165 p.1 CO2 became with a rate of 165! 11 CO2/h develops, which corresponds to about 5.4% of the original (not-immobilized) entire metabolic cell activity. The material of the immobilized yeast cells appeared beige with the macroscopic evaluation with amorphous particles; the microscopic investigation resulted in limited particles with irregular form. The Teilchengröl3e lay within the range of 300 to 900 lam; 1 min leaving untouched led to quantitative sedimentation. Example 17:35 g (damp mass) of a fresh paste from native cells of bacteria Erwinia arid those the enzyme L-Asparaginamidohydrolase with a specific activity of 100 lamol L-Asparaginsäure/min. g (damp mass) (37 C, pH 5.0 Snbstrat L-asparagine) contained, in 100 ml of a solution of a reactive polymer, which was manufactured as in the example 7, were suspended. Subsequently, the suspension was homogenized by intensive agitating, agitated 30 min as in example 16 weakly and left untouched afterwards 1 h at ambient temperature. After this time the viscose rayon, spongelike mass in 500-mlPolyethylenbehälter was recast and centrifuged with 500 g 30 min. Subsequently, the projection was poured off and the sediment with a filtration printing as subjected in example 7 with the difference that the mass was pressed kurzffistg, about 5 min, for the removal of the liquid part of the password of the reaküven polymer on a hydraulic press; the received fragile material was cut up and by a Fleischwolf with a special steel employment with 1 mm of large openings turned, over which the material was carrion-pressed in form of walzenförmigen granulates, then about the 3 h with 25° C at air dried, then three times with water decanted and finally over night in entmineralisiertem water pours was left. Altogether 8 g granulated firm material from immohilisierten lines with a specific activity were won by 64 l.tmol L-Asparaginsäure/g (Fenehtmasse) and irregular size of the walzenförmigen particles within the range of 1 to 3 mm. The material sedimentierte already during some ten seconds quantitatively. No. 388933 example 18:50 g (damp mass) of a paste from fresh native cells of Streptomyces of phaechromogenes with the enzyme Glucoseisomerase with a specific activity of 0,21 lxmol Fructose/min. g (damp mass) (60° C, pH 6.85, substrate glucose) in 200 ml 0.1 M NaC1-Lösung with pH 7.0 were suspended; the suspension was warmed up at short notice under continuous agitating 10 min to 70° C. Subsequently, the suspension was cooled down and centrifuged (relative centrifugal acceleration 5000 (g), min). Afterwards the projection was poured off and the sediment in 150 was suspended ml solution of the reactive polymer, which was manufactured as in example 7. Subsequently, for immobilization as in example 17 including centrifugation, short term pressing, meals and drying muddled with the difference that the developed, reproduced Granuli from immobilized cells with 50 was min-treated before ml on -28° C cooled down 2%iger adhesive solution (Ranagon) in acetone 3. Subsequently, the Granuli was sucked off sharply and continued to suck off on the frit still about 15 min, washed afterwards with approximately 1 1 0,05-M-Phosphatpuffer, sucked off again, suspended in 100 ml this Pufferl0sung and left untouched over night with +8° C. Altogether 20 g (damp mass) of the granulated firm material from immobilized cells with a specific activity were won by 0,1 lamol Fructose/g (damp mass) with particles of irregular size within the range of 0,5 to 3.0 mm. The material sedimentierte after some ten seconds quanütativ. Example 19; 45 g (damp mass) of a paste from fresh native cells of Aspergillus the Niger with the enzymes Glueoseoxidase and catalase with a specific activity of 0,1 Ixmol H202/min. mg (damp mass) were brought to one into 150 ml as in example 7 manufactured password of the reactive polymer. Afterwards to the immobilization as muddled in example 7 with the difference that the received reproduced Granuli was let dry at 40% of relative dampness (H2SO4) and ambient temperature 24 h. Afterwards the immobilized cells were brought into entmineralisiertes water and to 24 h with +8° C were let pour. Altogether 29 g (damp mass) became immobilized lines with a specific activity of 0,045 lamol H202/ml (feuch0 and irregular size of the particles won in the form of salts within the range of 0,5 to 3.0 mm. The material sedimentierte during some ten seconds quantitatively. Example 20; 20 g (damp mass) fresh, washed plant cells of Solanum aviculare (culture of the individual cells), which in hypertonischen environment of Saccharose-L0sung Solanum alkaloids and Phytosterine synthesize, in 100 ml one as in example 2 manufactured solution of a reactive polymer were suspended; the homogeneous suspension received after intensive agitating was recast into an aluminum bowl with a diameter of 15 cm and 4 h with -19° C in a Tiefkühlbox was stored. Afterwards the frozen reaction mixture was taken out of the Tiefkühlbox and poured over with approximately 50 ml 1-M-Phosphatpuffer with pH 5.7 and 0.75 M KC1; after 2 h leaving untouched the plant cell aggregates developed at ambient temperature were transferred into 1 I of the above buffer and several times with this buffer, in each case after qualitative sedimentation of the particles, were decanted. Finally the immobilized cells in the vacuum were sucked off, washed again on the frit with buffer solution and sucked off again as well as weighed in the vacuum (118 g). Afterwards the particles in 100 became ml a 8%igen (M/V) sterile aqueous saccharose solution brought in and three times 24 h agitated the suspension with 20° C with a magnet agitator, whereby in 24-hIntervallen in the saccharose solution after separating the aggregates extracelluläre production was determined by SolanumAlkaloiden and Physterin by HPLC chromatography (see Jirku et al., Biotechnol. Letters 3, No. Ä1981Ü 447). It was stated that in three the production of the above components remains repeated 24stündigen intervals with same employment at immobilized lines. Furthermore the particles were scanning electron microscope examined, whereby the gegenseiüge connection of the plant cells was proven. Beisoiel 21:30 g (damp mass) fresh, washed plant cells as in example 20 were suspended in 100 ml 0.05 M phosphate buffers with pH 6.0 and 0.75 M NCI. The homogeneous suspension of the cells a flocculation means (technical Polyethylenimin) in a quantity of 0,5 VOL became under agitating. - % admitted. After Durchrühren the suspension 1 h was calmly left untouched at ambient temperature, until visually ascertainable flocculation of the cells was present. To damage subsequently, the suspension careful, do the präformierten cell aggregates, onto a frit over-poured and over textile material slowly however thoroughly in the vacuum not sucked off. After sucking the surplus liquid off the material without washing was brought to one in 100 ml as into example 10 manufactured solution of a reactive polymer and the received suspension by careful, slow agitating was homogenized. After the homogenization the suspension 1 h was left untouched at ambient temperature; the further immobilization happened as in example 20 with the difference that the temperature amounted to during the freezing -25° C. After 4 h freezing was inferred the material from the Tiefkühlbox and in accordance with example processed with the difference that the thawing out time amounted to with Raumtemperamr 1 h. 20 g immobilized, washed and well ahgesaugte lines were won. Subsequently, the particles from immobilized cells transferred into the same medium as into example with the difference that the bio-synthesis of the Solanum alkaloids was accomplished and by Phytosterin under No. 388933 recirculation of the saccharose solution in a fluidized bed of the biocatalyst 5 - 24 h, whereby in 24-h-Intervallen in the saccharose solution the production of the Solanum alkaloids was determined and of Phytosterin as in example 20. It was stated that in five repeated 24-h-Intervallen the production as well as the production rhythm of the indicated components remain with same employment at immobilized cells. Example 22; Two solutions were manufactured of 25 each ml, the 0.1% (M/V) Polylysin. HCI with a molecule mass from 40,000 to 50,000 and/or 1% (M/V) Polylysin with a molecule mass of 26,200 contained. For the dissolution of the Polylysins with the molecule mass of 40 1300 to 50,000 distilled water was used and for the solution of the Polylysins with the molecule mass of 26,200,0.1 M-trichloroethylene-buffers with pH 0.8. Into each of the two Polylysinlösungen a 25% were admitted a ige solution by Glutaraldehyd in water in the way, dafl their concentration in the reaction mixture 0.3 VOL. - % in the case of the Polylysins with the molecule mass from 40,000 to 50,000 and/or 0ù5 VOL. - amounted to % in the case of the Polylysins with the molecule mass 26,200. The containers with the Reaktionsgemiseh were then brought on a Rotaüonsschüttelmaschine, with which the reaction mixtures 10 h were mixed continuously with 30° C. The speed of the polymerization and/or the education of the get'ärbten Schiff' bases as pursued in example 1 spektrophotometrisch with the difference that with the wavelength by 430 Nm one measured. After the indicated length of time into each of the solutions of the RH, active polymer 6 g (damp mass) were suspended fresh native yeasts Saccharomyces cerevisiae with Invertaseakävität and a specific activity of 14 gmol glucose/min. mg (dry weight) of the cells (30° C, pH 4.8 substrate saccharose) to a homogeneous suspension. The suspensions were mixed 1 h on a Laborshaker and afterwards 2 h were left untouched, on which the particles were abzentrifugiert, relative centrifugal acceleration (5000, 10 min); the sediments were brought in separately into an injection syringe without needle and the firm paste in roller form on aluminum foil was pressed out. The not washed reproduced particles at ambient temperature 6 h dry left and afterwards mechanically to particles of approximately same size homogenized and over night in water with 5° C pour let. The poured particles were then washed several times in the vacuum filtered, with water, weighed thoroughly sucked off and. 5.6 g (damp mass) were won particle with a specific activity of 276 p.mol glucose/min. g (damp mass) in the first case and/or 3.6 g (damp mass) particle with a specific Aküvität of 387,2 lamol Ghcose/min. g (damp mass) in the second case. The particles were present in both Fltllen in form of firm rollers with a diameter of 1.2 mm and a size in the poured condition within the range of 1,45 to 4 mm. The material sedimenäerte during some seconds quantitatively. g (damp mass) of the immobilized cells with the specific activity of 387,2 tmol glucose/min. g were suspended in 50 ml 0,5-M-Saccharose-Lösung in 0,05-N-Acetatpuffer with pH 4.9, whereby under continuous agitating with a slowly running anchor agitator at a number of revolutions by 100 rpm and a temperature of 30° C the enzymatic inversion of the saccharose was accomplished to a mixture by glucose and Fructose. The enzymatic transformation was quantitative on the indicated reaction conditions in 3 h. This procedure was repeated altogether ten times with same employment at biocatalysts, whereby after each terminated cycle of the repetitive enzymatic inversion the particles by Seihen by a PP filter separated, with which indicated buffer was washed and used again in the indicated kind. The middle degree of the enzymatic inversion with ten cycles of the repetitive use of the same beginning at immobilized cells amounted to 92.6%. Example 23: 50 was manufactured ml a 10%igen solution by technical L-Lysin (active substance content 88%) in 0,1-M-Tris-Puffer pH 8.2. Into this solution a 25% were admitted a ige solution by Glutaraldehyd in water in the way that its Konzentraüon in the reaction mixture 5 VOL. - amounted to %. The Reakäonsgemisch was then agitated continuously under the conditions and in the kind by example 22, whereby the reaction duration amounted to however 24 h. After this time in 50 ml the dark-brown solution of the reactive polymer 12 g (Fenchtmasse) were suspended fresh native cells of the same microorganism with the same enzymatic activity as in example 22. The suspension was fibrationsmi homogenized with a high-speed and poured then into a bowl made of aluminum foil and stored 24 h with -20° C in a Tiefläihlbox. Afterwards the bowl was taken out of the Tiefkühlbox and its contents with Ranmtemperatur thaw out was let spontaneous. Subsequently, those was centrifuged strongly viscose rayon, spongelike mixture (relative Zenlrifugalbeschleunigung 10,000, 15 min); the projection was poured off and the sediment was brought into " a lnjekUonsspfitze and as processed in example 22 with the difference that the drying process of the reproduced particles at air lasted 10 h. After filtration, washing and pouring the material as in example 22 2.8 g (damp mass) became particles with a specific activity at Invertase of 180 lamol Glucosedmin. g (damp mass) and a particle size won within the range of 1,2 to 3.7 mm. The material existed after pouring from spongelike, halfsoft rollers, which sedimentierten during some seconds quantitatively. No. 388933