WO1997029203A1 - Process for separating organic acids from a fermentation medium - Google Patents

Process for separating organic acids from a fermentation medium Download PDF

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Publication number
WO1997029203A1
WO1997029203A1 PCT/DE1997/000230 DE9700230W WO9729203A1 WO 1997029203 A1 WO1997029203 A1 WO 1997029203A1 DE 9700230 W DE9700230 W DE 9700230W WO 9729203 A1 WO9729203 A1 WO 9729203A1
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WIPO (PCT)
Prior art keywords
fermentation medium
acid
membrane device
fermentation
membrane
Prior art date
Application number
PCT/DE1997/000230
Other languages
German (de)
French (fr)
Inventor
Karl W. BÖDDEKER
Christian Schorm
Dario WINDMÖLLER
Original Assignee
Gkss-Forschungszentrum Geesthacht Gmbh
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Publication of WO1997029203A1 publication Critical patent/WO1997029203A1/en

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/42—Electrodialysis; Electro-osmosis ; Electro-ultrafiltration; Membrane capacitive deionization
    • B01D61/44—Ion-selective electrodialysis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/24—Dialysis ; Membrane extraction
    • B01D61/243—Dialysis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/47—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids

Definitions

  • the invention relates to a method for separating organic acids from a fermentation medium located in a fermentation device, the fermentation medium being guided to a membrane device in which the acid contained in the fermentation medium is separated.
  • electro-analytical processes In order to reduce the inhibition of microbial growth in a fermentation process by acids and to accelerate product formation, electro-analytical processes have recently been proposed which can also be operated with an active bioreactor.
  • the acids are removed from the reactor medium by means of electrodialysis and transferred to a second liquid circuit.
  • the acid-depleted solution is then returned to the reactor.
  • This method has serious disadvantages both in terms of the effectiveness and the complexity of the process.
  • the ion exchange membranes are permeable to Protons or acid molecules, which place a limit on their accumulation in the dialysate stream, ie, accumulation in the reactor medium (limited selectivity).
  • the electric field in the electrodi alys unit generally has a negative influence on the microorganisms, so that prior to the electrodi alysis the microorganisms are passed through a filter unit which, for example, is based on the principle of ultrafiltration or mi crofi 1 trati on is operated, separated and returned to the reactor (cell-free medium).
  • a filter unit which, for example, is based on the principle of ultrafiltration or mi crofi 1 trati on is operated, separated and returned to the reactor (cell-free medium).
  • the object is achieved according to the invention in that the membrane device is operated on the principle of Donnan dialysis with anion exchange membranes, the fermentation medium (feed) being guided in the manner of a cycle along the feed side of the membrane device and along the discharge side of the membrane device
  • Type of a circuit is a dialysate, which is adjusted to an alkaline pH by adding bases.
  • ions of the same sense of charge (anions) cross the anion exchange membranes in the opposite direction: the acid anions from the reactor medium into the dialysate (where they can be obtained in the form of the salt of the respective acid), the hydroxide ions from the Dialysate in the reactor medium (where they instantly neutralize the protons of the acid to water).
  • the proton permeability of the membranes which is disadvantageous in the case of electrodialysis, acts in the desired direction in the Donnan dialysis described here, by contributing to the complete discharge of the acids.
  • the advantages of the method according to the invention are essentially that the Donnan dialysis and the bioprocess coupled to it can significantly reduce the outlay in equipment and the energy requirement compared to the previous electrodialysis processes.
  • the fact that the process according to the invention permits complete discharge of the acids and that the acids (in the form of the corresponding salts) can be enriched in the dialysate also helps.
  • the rate of acid discharge from the bioprocess can be controlled by adjusting the pH (the base concentration) in the dialysis sl sl.
  • the amount of acid withdrawn from the fermentation medium via the membrane device can be controlled in such a way that on the one hand a maximum of acid is produced in the fermentation medium by the microorganisms contained therein and on the other hand a maximum of microorganisms in the Fermentation medium itself arises.
  • Such an advantageous process control takes into account the fact that the amount of acid, which is generated by the microorganisms in the fermentation medium, ie acid concentration during the fermentation, reaches a maximum value which then opposes the cell division of the microorganisms, whereby with the proposed procedure, the acid concentration is always kept so high by withdrawing the acid that a maximum of newly forming microorganisms which generate the acid is maintained.
  • the example relates to the intracellular formation of vitamin B, 2 De i simultaneous extracellular formation of propionic acid by propionibacteria.
  • the following show:
  • FIG. 3 shows a graphical representation of the course of a vitamin B j ⁇ fermentation with growth-dependent Donnan dialysis: in comparison to the representation of FIG. 2, Donnan dialysis was used periodically before the microorganisms died significantly.
  • the basic structure of such an arrangement 10 is described with reference to the block diagram of an arrangement 10 for carrying out the method shown in FIG. 1.
  • This comprises at least one fermentation device 11, in which a fermentation medium 12 is contained, which will be discussed in more detail below.
  • the fermentation device 11 is connected to the feed side 15 of a membrane device 13 operating on the principle of Donnan dialysis, a connection to the fermentation device 11 being provided from the feed side 15, via which the acid-depleted fermentation medium 12 enters the fermentations ⁇ device 11 is returned.
  • the discharge side 16 of the membrane device 13 is connected to a container 27 or device in which an alkaline dialysate 17 is received.
  • the dialysate 17 is fed via a connection to the discharge side 16 of the membrane device 13, the acid or salt-resistant dialysate 17 in turn being fed back into the container 27 from the discharge side 16 of the membrane device 13.
  • the transport of the fermentation medium 12 from the fermentation device 11 to the membrane device 13 and the transport of the dialysate 17 from the container 27 to the membrane device 13 is carried out by respective pumps 24, 25, which are suitably controlled, which is shown in FIG. 1 by the dashed lines, which are connected to a detection and control device 26, which will be discussed further below.
  • Both the container 27 with the dialysate 17 and the fermentation device 11 with the fermentation medium 12 can be suitably temperature-controlled by means of temperature control devices 20, 21 connected to them, whereby the temperature in the respective media can be controlled by the detection and control device 26, which by the dashed line in Fig. 1 is shown schematically.
  • the fermentation device 11 is also connected to containers in which neutralizing agents 18, 19 are contained, for example in one phosphoric acid, in the other ammonia solution in order to adjust the pH of the fermentation medium 12, which is detected by the pH value detection device 28 and is given to the detection and control device 26, which is shown by the dashed line.
  • the temperature of the fermentation medium 12 is also detected by a temperature detection device 29, the signals of which are also sent to the detection and control device 26, which is also shown by a broken line.
  • a motor-driven agitator 30, which can optionally also be controlled by the detection and control device 26, ensures that the fermentation medium 12 in the fermentation device 11 is kept in constant motion during the execution of the method.
  • the vitamin B, o fermentation with Propioni bacteri was first described here as an exemplary bioprocess.
  • freudenreichi i (DSM 20271) chosen.
  • Propionibacteria utilize glucose and others that are strain-specific Carbohydrates including propionic acid and vitamin B, 2 (QUESADA-CHANTO 1993).
  • the propionic acid is released to the surrounding medium and reduced, depending on its concentration, the growth of the bacteria in the fermentation medium 12.
  • the bacterial density during the fermentation reaches a maximum value which is determined by the acid concentration. 2 shows the bacterial density (biomass) and the propionic acid concentration in the course of the fermentation.
  • the Donnan dialysis was started before the significant reduction in cell density and operated for a few hours.
  • the acid 14 By withdrawing the acid 14, a continuously increased cell density and also an increased propionic acid production could be achieved.
  • the cell density was increased from 5.6 g / 1 to 8.1 g / 1, while the acid concentration took the course shown in FIG. 3 in accordance with the operating intervals of the Donnan dialysis.
  • the fermentation medium 12 is conveyed directly along the feed side 15 of the membrane device 13 operated according to the principle of Donnan dialysis, specifically in unfilled form, the organic acid 14 being transferred through the ion exchange membranes into the dialysate 17, and the dialysate 17 being passed along the discharge side 16 of the membrane device 13 in the manner of a cycle.
  • the acid-depleted fermentation medium 12 is then fed back into the fermentation device 11, and the acid- or salt-enriched dialysate is returned to the container or the device 27.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Water Supply & Treatment (AREA)
  • Urology & Nephrology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

The invention proposes a process for the separation of organic acids (14) from a fermentation medium (12) contained in a fermentation device (11). The fermentation medium (12) is supplied onto a membrane device (13) in which the acid (14) contained in the fermentation medium (12) is separated. The membrane device (13) works according to the principle of Donnan dialysis through anion exchanger membranes. The fermentation medium (12) (supply) is circulated along the supply side (15) of the membrane device (13) while a dialysate (17) is circulated along the outlet side (16) of the membrane device (13), in which the acid (14) traversing the membrane (13) is enriched as salt.

Description

Verfahren zur Separierung organischer Säuren aus einem Fermentationsmedi umProcess for separating organic acids from a fermentation medium
Beschrei bungDescription
Die Erfindung betrifft ein Verfahren zur Separierung organischer Säuren aus einem in einer Fermentationsein¬ richtung befindlichen Fermentationsmedium, wobei das Fermentationsmedium auf eine Membraneinrichtung geführt wird, in der die im Fermentationsmedium enthaltene Säure separiert wird.The invention relates to a method for separating organic acids from a fermentation medium located in a fermentation device, the fermentation medium being guided to a membrane device in which the acid contained in the fermentation medium is separated.
Die Gewinnung organischer Säuren aus verdünnten wäss¬ rigen Lösungen ist mit herkömmlichen Methoden wie der Destillation, der Rektifikation, der Fl üssi g-Fl üs- si g-Extraktion und ähnlichen Verfahren prozeßtechnisch sehr aufwendig bzw. bei komplexen Ausgangsgemischen häufig sehr unselektiv. Keines der herkömmlichen Ver¬ fahren kann überdies mit einem aktiven Fermentations¬ prozeß gekoppelt werden. Gerade bei biologischen Produktionsverfahren verringert sich jedoch häufig die Stoffwechsel akti vi tat der Mikroorganismen mit zunehmen¬ der Säurekonzentration im Reaktor. Aufgrund dieser Eigenschaft wird die Produktivität und die maximal erreichbaren Zeil- und Produktkonzentrationen durch die mikrobiell produzierten organischen Säuren l imitiert. Beispiele für biologische Verfahren mit Produkthemmung durch Säuren sind u.a. Essigsäure-Fermentation mit Acetobacter aceti, die fermentative Milchsäuregewinnung mit Lactobacillus casei und die Vitamin B^-Gewi nnung mit Propi onsäurebakterien .The extraction of organic acids from dilute aqueous solutions using conventional methods such as distillation, rectification, liquid-liquid extraction and similar processes is very complex in terms of process technology or is often very unselective in the case of complex starting mixtures. Furthermore, none of the conventional methods can be coupled with an active fermentation process. Especially with biological However, production processes often reduce the metabolic activity of the microorganisms with increasing acid concentration in the reactor. Because of this property, the productivity and the maximum achievable line and product concentrations are imitated by the microbially produced organic acids. Examples of biological processes with product inhibition by acids include acetic acid fermentation with Acetobacter aceti, fermentative lactic acid extraction with Lactobacillus casei and vitamin B ^ extraction with propionic acid bacteria.
Zur Gewinnung der produzierten Säuren und parallel auftretender Stoffwechsel produkte sind aufgrund der geringen Produktkonzentrationen in der Regel eine Reihe von Verfahrensschritten nötig, die die fermentative Stoffgewinnung im Vergleich mit chemischen Syntheseme¬ thoden sehr zeit- und kostenintensiv werden lassen. Die Nachteile, die mit der Produkthemmung verbunden sind, werden bisher weitgehend hingenommen bzw. durch Zugabe pH-regelnder Reagenzien nur unzureichend vermindert oder durch ein vergrößertes Reaktionsvolumen kompensiert.In order to obtain the acids produced and metabolic products occurring in parallel, due to the low product concentrations, a number of process steps are generally necessary which make fermentative material production very time-consuming and cost-intensive in comparison with chemical synthesis methods. The disadvantages associated with product inhibition have so far largely been accepted or only insufficiently reduced by adding pH-regulating reagents or compensated for by an increased reaction volume.
Um die Hemmung des mikrobiellen Wachstums in einem Fermentationsprozeß durch Säuren zu vermindern und die Produktbildung zu forcieren, sind neuerdings Elektro- di alyseverfahren vorgeschlagen worden, die auch mit einem aktiven Bioreaktor betrieben werden können. Mittels Elektrodi alyse werden die Säuren dem Reaktorme¬ dium entzogen und in einen zweiten Flüssigkeitskreislauf überführt. Die säureabgereichte Lösung wird anschließend dem Reaktor wieder zugeführt. Sowohl bezüglich der Wirksamkeit als auch des Verfahrensaufwandes hat dieses Verfahren schwerwiegende Nachteile. Zum einen weisen die Ionenaustauschermembranen eine Durchlässigkeit für Protonen bzw. Säuremoleküle auf, die deren Anreicherung im Di alysatstrom, d.h. Abreicherung im Reaktormedium, eine Grenze setzen (begrenzte Selektivität) . Zum anderen hat das elektrische Feld in der El ektrodi alyseei nhei t im allgemeinen einen negativen Einfluß auf die Mikroorga¬ nismen, so daß vor der El ektrodi alyse die Mikroorganis¬ men durch eine Filtereinheit, die beispielsweise nach dem Prinzip der Ultrafiltration oder der Mi krofi 1 trati on betrieben wird, abgetrennt und dem Reaktor wieder zugeführt werden müssen (zellfreies Medium) . Mit der El ektrodi al yse kann die Produktivität von Bioprozessen zwar verbessert werden, jedoch mit beschränktem Wir¬ kungsgrad und unter Inkaufnahme einer aufwendigen Anlagenkonzeption mit zwei hi nterei nandergeschal teten Membranverfahren (1. Abtrennung der Mikroorganismen, 2. El ektrodi alyse) und entsprechend hohen Kosten für die Investition und das Betreiben derartiger Anlagen.In order to reduce the inhibition of microbial growth in a fermentation process by acids and to accelerate product formation, electro-analytical processes have recently been proposed which can also be operated with an active bioreactor. The acids are removed from the reactor medium by means of electrodialysis and transferred to a second liquid circuit. The acid-depleted solution is then returned to the reactor. This method has serious disadvantages both in terms of the effectiveness and the complexity of the process. On the one hand, the ion exchange membranes are permeable to Protons or acid molecules, which place a limit on their accumulation in the dialysate stream, ie, accumulation in the reactor medium (limited selectivity). On the other hand, the electric field in the electrodi alys unit generally has a negative influence on the microorganisms, so that prior to the electrodi alysis the microorganisms are passed through a filter unit which, for example, is based on the principle of ultrafiltration or mi crofi 1 trati on is operated, separated and returned to the reactor (cell-free medium). With the electrodialysis, the productivity of bioprocesses can be improved, however, with a limited degree of efficiency and with the acceptance of a complex plant design with two interconnected membrane processes (1st separation of the microorganisms, 2nd electrodialysis) and correspondingly high Cost of investing and operating such systems.
Es ist somit Aufgabe der vorliegenden Erfindung, ein Verfahren der eingangs genannten Art zu schaffen, das die erheblichen Nachteile bisheriger Verfahren dieser Art nicht hat, das einfach und sehr wirksam und mit hoher Selektivität durchführbar ist und das im Vergleich zu bisherigen Verfahren dieser Art kostengünstig durch¬ führbar i st .It is therefore an object of the present invention to provide a method of the type mentioned which does not have the considerable disadvantages of previous methods of this type, which is simple and very effective and can be carried out with high selectivity and which is inexpensive in comparison to previous methods of this type ¬ feasible
Gelöst wird die Aufgabe gemäß der Erfindung dadurch, daß die Membraneinrichtung nach dem Prinzip der Donnan- Dialyse mit Anionenaustauschermembranen betrieben wird, wobei das Fermentationsmedium (Zulauf) nach Art eines Kreislaufs längs der Zufuhrseite der Membraneinrichtung geführt wird und längs der Abführseite der Membranein¬ richtung nach Art eines Kreislaufs ein Dialysat geführt wird, welches durch Zugabe von Basen auf einen alka¬ lischen pH-Wert eingestellt ist. In einem solchen bi-ionischen System durchqueren Ionen gleichen Ladungssinnes (Anionen) in entgegengesetzter Richtung die Ani onenaustauschermembranen : die Säurean- ionen aus dem Reaktormedium in das Dialysat (wo sie in Form des Salzes der jeweiligen Säure gewonnen werden können), die Hydroxidionen aus dem Dialysat in das Reaktormedium (wo sie die Protonen der Säure augen¬ blicklich zu Wasser neutralisieren). Die bei der Elek- trodialyse nachteilige Protonendurchlässigkeit der Membranen wirkt bei der hier beschriebenen Donnan- Dialyse in die gewünschte Richtung, indem sie zum vollständigen Austrag der Säuren beiträgt.The object is achieved according to the invention in that the membrane device is operated on the principle of Donnan dialysis with anion exchange membranes, the fermentation medium (feed) being guided in the manner of a cycle along the feed side of the membrane device and along the discharge side of the membrane device Type of a circuit is a dialysate, which is adjusted to an alkaline pH by adding bases. In such a bi-ionic system, ions of the same sense of charge (anions) cross the anion exchange membranes in the opposite direction: the acid anions from the reactor medium into the dialysate (where they can be obtained in the form of the salt of the respective acid), the hydroxide ions from the Dialysate in the reactor medium (where they instantly neutralize the protons of the acid to water). The proton permeability of the membranes, which is disadvantageous in the case of electrodialysis, acts in the desired direction in the Donnan dialysis described here, by contributing to the complete discharge of the acids.
Die Vorteile des erfindungsgemäßen Verfahrens liegen im wesentlichen darin, daß durch die Donnan-Di alyse und des mit ihr gekoppelten Bioprozesses gegenüber den bishe¬ rigen El ektrodi alyseverfahren der apparative Aufwand und der Energiebedarf erheblich reduziert werden können. Zur Erhöhung der Produktivität des Bioprozesses, auch hinsichtlich der gebildeten Säuren, trägt bei, daß das erfindungsgemäße Verfahren einen vollständigen Austrag der Säuren gestattet, und daß darüber hinaus die Säuren (in Form der entsprechenden Salze) im Dialysat angerei¬ chert werden können.The advantages of the method according to the invention are essentially that the Donnan dialysis and the bioprocess coupled to it can significantly reduce the outlay in equipment and the energy requirement compared to the previous electrodialysis processes. To increase the productivity of the bioprocess, also with regard to the acids formed, the fact that the process according to the invention permits complete discharge of the acids and that the acids (in the form of the corresponding salts) can be enriched in the dialysate also helps.
Ein weiterer wesentlicher Vorteil der erfindungsgemäßen Verfahrenskombination ist, daß die Geschwindigkeit des Säureaustrags aus dem Bioprozeß durch Einstellung des pH-Wertes (der Basenkonzentration) im Di alysatkrei sl auf kontrollierbar ist. Im Sinne der Erfindung ist die über die Membraneinrichtung dem Fermentationsmedium entzogene Säuremenge pro Zeiteinheit derart steuerbar, daß im Fermentationsmedium durch die darin enthaltenen Mikro¬ organismen einerseits ein Maximum an Säure produziert wird, und andererseits ein Maximum an Mikroorganismen im Fermentationsmedium selbst entsteht. Mit einer derar¬ tigen vorteilhaften Verfahrenssteuerung wird dem Umstand Rechnung getragen, daß an sich die Säuremenge, die von den Mikroorganismen im Fermentationsmedium erzeugt wird, d.h. Säurekonzentration im Verlauf der Fermentation, einen maximalen Wert erreicht, der der Zellteilung der Mikroorganismen dann gegenläufig ist, wobei mit der vorgeschlagenen Verfahrensführung die Säurekonzentration durch Entzug der Säure immer derart groß gehalten wird, daß ein Maximum an sich neu bildenden Mikroorganismen, die die Säure erzeugen, aufrechterhalten wird.Another significant advantage of the process combination according to the invention is that the rate of acid discharge from the bioprocess can be controlled by adjusting the pH (the base concentration) in the dialysis sl sl. For the purposes of the invention, the amount of acid withdrawn from the fermentation medium via the membrane device can be controlled in such a way that on the one hand a maximum of acid is produced in the fermentation medium by the microorganisms contained therein and on the other hand a maximum of microorganisms in the Fermentation medium itself arises. Such an advantageous process control takes into account the fact that the amount of acid, which is generated by the microorganisms in the fermentation medium, ie acid concentration during the fermentation, reaches a maximum value which then opposes the cell division of the microorganisms, whereby with the proposed procedure, the acid concentration is always kept so high by withdrawing the acid that a maximum of newly forming microorganisms which generate the acid is maintained.
Die Erfindung wird nun unter Bezugnahme auf die beige¬ fügten Zeichnungen anhand eines Ausführungsbeispieles eingehend beschrieben. Das Beispiel betrifft die intra¬ zelluläre Bildung von Vitamin B,2 Dei gleichzeitiger extrazellulärer Bildung von Propionsaure durch Propioni- bakterien. Im folgenden zeigen:The invention will now be described in detail with reference to the accompanying drawings using an exemplary embodiment. The example relates to the intracellular formation of vitamin B, 2 De i simultaneous extracellular formation of propionic acid by propionibacteria. The following show:
Fig. 1 in Form eines Blockschaltbildes den schema¬ tischen Aufbau einer Anordnung zur Ausführung des Verfahrens,1 in the form of a block diagram the schematic structure of an arrangement for executing the method,
Fig. 2 in graphischer Darstellung den Verlauf einer Vi tami n-B, „-Fermentati on vor (< 185 h) und nach (> 185 h) der Zuschaltung der Donnan-Di alyse,2 shows a graphical representation of the course of a vitamin t-B, “fermentation before (<185 h) and after (> 185 h) the connection of the Donnan dialysis,
Fig. 3 in graphischer Darstellung den Verlauf einer Vitamin Bj^-Fermentati on mit wachstumsabhän¬ giger Donnan-Dialyse: im Vergleich zur Dar¬ stellung von Fig. 2 erfolgte der Einsatz der Donnan-Dialyse periodisch jeweils vor dem signifikanten Absterben der Mikroorganismen. Unter Bezugnahme auf das in Fig. 1 dargestellte Block¬ schaltbild einer Anordnung 10 zur Ausführung des Ver¬ fahrens wird der prinzipielle Aufbau einer derartigen Anordnung 10 beschrieben.3 shows a graphical representation of the course of a vitamin B j ^ fermentation with growth-dependent Donnan dialysis: in comparison to the representation of FIG. 2, Donnan dialysis was used periodically before the microorganisms died significantly. The basic structure of such an arrangement 10 is described with reference to the block diagram of an arrangement 10 for carrying out the method shown in FIG. 1.
Diese umfaßt wenigstens eine Fermentationseinrichtung 11, in der ein Fermentationsmedium 12 enthalten ist, auf das eingehender noch weiter unten eingegangen wird. Die Fermentationseinrichtung 11 ist mit der Zufuhrseite 15 einer nach dem Prinzip der Donnan-Dialyse arbeitenden Membraneinrichtung 13 verbunden, wobei von der Zufuhr¬ seite 15 wiederum eine Verbindung zur Fermentationsein¬ richtung 11 vorgesehen ist, über die das säureabgerei - cherte Fermentationsmedium 12 in die Fermentations¬ einrichtung 11 zurückgeführt wird.This comprises at least one fermentation device 11, in which a fermentation medium 12 is contained, which will be discussed in more detail below. The fermentation device 11 is connected to the feed side 15 of a membrane device 13 operating on the principle of Donnan dialysis, a connection to the fermentation device 11 being provided from the feed side 15, via which the acid-depleted fermentation medium 12 enters the fermentations ¬ device 11 is returned.
Die Abfuhrseite 16 der Membraneinrichtung 13 ist mit einem Behälter 27 bzw. Einrichtung verbunden, in der ein alkalisches Dialysat 17 aufgenommen wird. Das Dialysat 17 wird über eine Verbindung auf die Abführseite 16 der Membraneinrichtung 13 geführt, wobei das säure- bzw. sal zangerei chte Dialysat 17 wiederum von der Abführseite 16 der Membraneinrichtung 13 zurück in den Behälter 27 geführt wird.The discharge side 16 of the membrane device 13 is connected to a container 27 or device in which an alkaline dialysate 17 is received. The dialysate 17 is fed via a connection to the discharge side 16 of the membrane device 13, the acid or salt-resistant dialysate 17 in turn being fed back into the container 27 from the discharge side 16 of the membrane device 13.
Der Transport des Fermentationsmediums 12 von der Fermentationseinrichtung 11 zur Membraneinrichtung 13 und der Transport des Dialysats 17 vom Behälter 27 zur Membraneinrichtung 13 wird durch jeweilige Pumpen 24, 25 ausgeführt, die geeignet gesteuert werden, was in Fig. 1 mittels der gestrichelten Linien dargestellt ist, die mit einer Erfassungs- und Steuereinrichtung 26 verbunden sind, auf die noch weiter unten eingegangen wird. Sowohl der Behälter 27 mit dem Dialysat 17 als auch die Fermentationseinrichtung 11 mit dem Fermentationsmedium 12 können geeignet durch jeweils damit verbundene Temperierungseinrichtungen 20, 21 temperiert werden, wobei die Temperatur in den jeweiligen Medien durch die Erfassungs- und Steuereinrichtung 26 gesteuert werden kann, was durch die gestrichelte Linie in Fig. 1 sche¬ matisch dargestellt ist.The transport of the fermentation medium 12 from the fermentation device 11 to the membrane device 13 and the transport of the dialysate 17 from the container 27 to the membrane device 13 is carried out by respective pumps 24, 25, which are suitably controlled, which is shown in FIG. 1 by the dashed lines, which are connected to a detection and control device 26, which will be discussed further below. Both the container 27 with the dialysate 17 and the fermentation device 11 with the fermentation medium 12 can be suitably temperature-controlled by means of temperature control devices 20, 21 connected to them, whereby the temperature in the respective media can be controlled by the detection and control device 26, which by the dashed line in Fig. 1 is shown schematically.
Die Fermentationseinrichtung 11 ist zudem noch mit Behältern verbunden, in denen Neutralisationsmittel 18, 19 enthalten sind, beispielsweise im einen Phosphorsäu¬ re, im anderen Ammoniaklösung, um den pH-Wert des Fermentationsmediums 12 einzustellen, der durch die pH-Werterfassungeinrichtung 28 erfaßt wird und auf die Erfassungs- und Steuereinrichtung 26 gegeben wird, was durch die gestrichelte Linie dargestellt wird. Ebenfalls erfaßt wird die Temperatur des Fermentationsmediums 12 durch eine Temperaturerfassungseinrichtung 29, deren Signale ebenfalls auf die Erfassungs- und Steuerein¬ richtung 26 gegeben wird, was ebenfalls durch eine gestrichelte Linie dargestellt ist.The fermentation device 11 is also connected to containers in which neutralizing agents 18, 19 are contained, for example in one phosphoric acid, in the other ammonia solution in order to adjust the pH of the fermentation medium 12, which is detected by the pH value detection device 28 and is given to the detection and control device 26, which is shown by the dashed line. The temperature of the fermentation medium 12 is also detected by a temperature detection device 29, the signals of which are also sent to the detection and control device 26, which is also shown by a broken line.
Ein motorgetriebenes Rührwerk 30, das gegebenenfalls ebenfalls von der Erfassungs- und Steuereinrichtung 26 gesteuert werden kann, sorgt dafür, daß das Fermentati¬ onsmedium 12 in der Fermentationseinrichtung 11 bei der Ausführung des Verfahrens fortwährend in Bewegung gehalten wird.A motor-driven agitator 30, which can optionally also be controlled by the detection and control device 26, ensures that the fermentation medium 12 in the fermentation device 11 is kept in constant motion during the execution of the method.
Zur Ausführung des erfindungsgemäßen Verfahrens wurde hier zunächst als beispielhafter Bioprozeß die Vitamin B, o—Fermentati on mit Propioni bacteri um freudenrei chi i ssp. freudenreichi i (DSM 20271) gewählt. Propionibak- terien verwerten Glukose und stammspezifisch andere Kohlenhydrate u.a. zu Propionsaure und Vitamin B,2 (QUESADA-CHANTO 1993). Die Propionsaure wird an das umgebende Medium abgegeben und vermindert, in Abhängig¬ keit von deren Konzentration, das Wachstum der Bakterien im Fermentationsmedium 12. Dadurch erreicht die Bakte¬ riendichte im Verlauf der Fermentation einen maximalen Wert, der durch die Säurekonzentration bestimmt wird. In Fig. 2 ist die Bakteriendichte (Biomasse) und die Propi onsäurekonzentrati on im Verlauf der Fermentation dargestellt. Nachdem die Bakteriendichte durch die entstandene Säure abnahm, setzte im Verlaufe des Ver¬ fahrens die Donnan-Dialyse ein (gestrichelte Linie) und verringerte innerhalb von 20 Stunden die Propi onsäure¬ konzentrati on in der Fermentationseinrichtung 11 von 31 auf 6,5 g/1. Durch den Entzug der Säure 14 wurden die Bakterien zur weiteren Zellteilung und Säureproduktion animi ert .In order to carry out the method according to the invention, the vitamin B, o fermentation with Propioni bacteri was first described here as an exemplary bioprocess. freudenreichi i (DSM 20271) chosen. Propionibacteria utilize glucose and others that are strain-specific Carbohydrates including propionic acid and vitamin B, 2 (QUESADA-CHANTO 1993). The propionic acid is released to the surrounding medium and reduced, depending on its concentration, the growth of the bacteria in the fermentation medium 12. As a result, the bacterial density during the fermentation reaches a maximum value which is determined by the acid concentration. 2 shows the bacterial density (biomass) and the propionic acid concentration in the course of the fermentation. After the bacterial density decreased due to the acid produced, Donnan dialysis started in the course of the process (dashed line) and reduced the propionic acid concentration in the fermentation device 11 from 31 to 6.5 g / l within 20 hours . By withdrawing acid 14, the bacteria were animated to further cell division and acid production.
Bei der Verfahrensführung gemäß der Darstellung von Fig. 3 wurde die Donnan-Dialyse jeweils vor der signifikanten Reduktion der Zelldichte begonnen und für einige Stunden betrieben. Durch den Entzug der Säure 14 konnte eine fortlaufend erhöhte Zelldichte und eine ebenfalls erhöhte Propi onsäureproduktion erzielt werden. Die Zelldichte wurde bei dieser Verfahrensführung von 5,6 g/1 auf 8,1 g/1 erhöht, während die Säurekonzentration entsprechend den Betriebsintervallen der Donnan-Dialyse den in Fig. 3 dargestellten Verlauf nahm.3, the Donnan dialysis was started before the significant reduction in cell density and operated for a few hours. By withdrawing the acid 14, a continuously increased cell density and also an increased propionic acid production could be achieved. In this procedure, the cell density was increased from 5.6 g / 1 to 8.1 g / 1, while the acid concentration took the course shown in FIG. 3 in accordance with the operating intervals of the Donnan dialysis.
Bei den vorangehend beschriebenen Verfahrensführungen bzw. den abgewandelten Verfahrensführungen mittels der Anordnung 10 gemäß Fig. 1 gilt allgemein, daß das Fermentationsmedium 12 direkt längs der Zufuhrseite 15 der nach dem Prinzip der Donnan-Dialyse betriebenen Membraneinrichtung 13 gefördert wird, und zwar in unfi 1 tri erter Form, wobei die organische Säure 14 durch die Ionenaustauschermembranen in das Dialysat 17 über¬ führt wird, und wobei das Dialysat 17 nach Art eines Kreislaufs längs der Abführseite 16 der Membraneinrich¬ tung 13 geführt wird. Das säureabgerei cherte Fermenta¬ tionsmedium 12 wird dann wieder in die Fermentations¬ einrichtung 11, und das säure- bzw. salzangereicherte Dialysat zum Behälter bzw. der Einrichtung 27 zurückge¬ führt. Durch prozeßtechnische Regelung für die Schalt¬ zustände und die Förderleistungen der Umwälzpumpen für den Kreislauf des Fermentationsmediums 12 sowie des Kreislaufs des Dialysats 17 mittels der Erfassungs- und Steuereinrichtung 26, die beispielsweise aus einem Prozeßrechner bestehen kann, kann die Abreicherung des Fermentationsmediums 12 von Säure 14, und damit die Produktivität des Gesamtverfahrens, gesteuert werden. In the case of the process procedures described above or the modified process procedures by means of the arrangement 10 according to FIG. 1, it generally applies that the fermentation medium 12 is conveyed directly along the feed side 15 of the membrane device 13 operated according to the principle of Donnan dialysis, specifically in unfilled form, the organic acid 14 being transferred through the ion exchange membranes into the dialysate 17, and the dialysate 17 being passed along the discharge side 16 of the membrane device 13 in the manner of a cycle. The acid-depleted fermentation medium 12 is then fed back into the fermentation device 11, and the acid- or salt-enriched dialysate is returned to the container or the device 27. Process control for the switching states and the delivery rates of the circulation pumps for the circuit of the fermentation medium 12 and the circuit of the dialysate 17 by means of the detection and control device 26, which can consist, for example, of a process computer, can deplete the fermentation medium 12 from acid 14 , and thus the productivity of the overall process.
Bezugszeichenl isteReference numerals
10 Anordnung10 arrangement
11 Fermentationseinrichtung11 fermentation device
12 Fermentationsmedium12 fermentation medium
13 Membraneinrichtung13 membrane device
14 Säure14 acid
15 Zuführsei te/Membraneinri chtung15 Feed side / membrane device
16 Abführsei te/Membraneinri chtung16 discharge side / diaphragm device
17 Dialysat17 dialysate
18 Neutralisationsmittel18 neutralizing agent
19 Neutralisationsmittel19 neutralizing agent
20 Temperatureinrichtung20 temperature device
21 Temperatureinrichtung21 temperature device
22 Pumpe22 pump
23 Pumpe23 pump
24 Pumpe24 pump
25 Pumpe25 pump
26 Erfassungs- und Steuereinrichtung26 Detection and control device
27 Dialysatbehäl ter27 dialysate container
28 pH-Wert Erfassungseinrichtung28 pH value detection device
29 Temperaturerfassungseinrichtung29 Temperature detection device
30 motorgetriebenes Rührwerk 30 motorized agitator

Claims

Patentansprüche claims
1. Verfahren zur Separierung organischer Säuren aus einem in einer Fermentati onsei nrichung befindlichen Fermentationsmedium, wobei das Fermentationsmedium auf eine Membraneinrichtung geführt wird, in der die im Fermentationsmedium enthaltene Säure separiert wird, dadurch gekennzeichnet, daß die Membraneinrichtung (13) nach dem Prinzip der Donnan-Dialyse betrieben wird, wobei das Fermentationsmedium (12) (Zulauf) nach Art eines Kreislaufs längs der Zuführseite (15) der Mem- branei nrichtung (13) geführt wird und längs der Abführ¬ seite (16) der Membraneinrichtung (13) nach Art eines Kreislaufs ein Dialysat (17) geführt wird, in dem die die Membran (13) durchquerende Säure (14) als Salz angereichert wird. 1. A method for separating organic acids from a fermentation medium located in a fermentation medium, the fermentation medium being passed onto a membrane device in which the acid contained in the fermentation medium is separated, characterized in that the membrane device (13) according to the Donnan principle -Dialysis is operated, the fermentation medium (12) (feed) being guided in the manner of a circuit along the feed side (15) of the membrane device (13) and along the discharge side (16) of the membrane device (13) according to Art of a circuit, a dialysate (17) is passed in which the acid (14) passing through the membrane (13) is enriched as a salt.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß die über die Membraneinrichtung (13) dem Fermenta¬ tionsmedium (12) entzogene Säurenmenge pro Zeit derart steuerbar ist, daß im Fermentationsmedium (12) durch die darin enthaltenem Mikroorganismen einerseits ein Maximum an Säure (14) produziert wird und andererseits ein Maximum an Mikroorganismen im Fermentationsmedium sei bst .2. The method according to claim 1, characterized in that the amount of acid withdrawn via the membrane device (13) from the fermentation medium (12) is controllable per time in such a way that in the fermentation medium (12) the microorganisms contained therein on the one hand a maximum of acid ( 14) is produced and on the other hand a maximum of microorganisms in the fermentation medium.
3. Verfahren nach einem oder mehreren der Ansprüche 1 oder 2, dadurch gekennzeichnet, daß der pH-Wert des Fermentationsmediums (12) während des Verfahrensver¬ laufes auf einem vorbestimmbaren Wert gehalten wird.3. The method according to one or more of claims 1 or 2, characterized in that the pH of the fermentation medium (12) is kept at a predetermined value during the course of the process.
4. Verfahren nach Anspruch 3, dadurch gekennzeichnet, daß der pH-Wert des Fermentationsmediums (12) durch geeignete Steuerung der Entnahmemenge der Säure pro Zeiteinheit auf dem vorbestimmbaren Wert gehalten wird.4. The method according to claim 3, characterized in that the pH of the fermentation medium (12) is kept at a predetermined value by suitable control of the amount of acid removed per unit of time.
sch/we sh / we
PCT/DE1997/000230 1996-02-09 1997-02-06 Process for separating organic acids from a fermentation medium WO1997029203A1 (en)

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DE19604700A DE19604700C1 (en) 1996-02-09 1996-02-09 Organic acid production process uses Donnan-dialysis anion exchanger-membrane

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FR2934264B1 (en) * 2008-07-22 2012-07-20 Arkema France MANUFACTURE OF VINYL ESTERS FROM RENEWABLE MATERIALS, VINYL ESTERS OBTAINED AND USES THEREOF

Citations (5)

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Publication number Priority date Publication date Assignee Title
EP0230021A2 (en) * 1985-12-20 1987-07-29 Hüls Aktiengesellschaft Continuous process for the production of organic acids by means of fermentation
JPS637345B2 (en) * 1980-07-04 1988-02-16 Hitachi Ltd
US4775478A (en) * 1986-09-03 1988-10-04 Basf Aktiengesellschaft Process for removing acid from cathodic electrocoating baths
EP0346983A2 (en) * 1988-06-14 1989-12-20 Coöperatieve Vereniging Suiker Unie U.A. A process for the fermentative preparation of organic acids
WO1995002716A1 (en) * 1993-07-12 1995-01-26 Aharon Eyal A process for the production of water-soluble salts of carboxylic and amino acids

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS637345B2 (en) * 1980-07-04 1988-02-16 Hitachi Ltd
EP0230021A2 (en) * 1985-12-20 1987-07-29 Hüls Aktiengesellschaft Continuous process for the production of organic acids by means of fermentation
US4775478A (en) * 1986-09-03 1988-10-04 Basf Aktiengesellschaft Process for removing acid from cathodic electrocoating baths
EP0346983A2 (en) * 1988-06-14 1989-12-20 Coöperatieve Vereniging Suiker Unie U.A. A process for the fermentative preparation of organic acids
WO1995002716A1 (en) * 1993-07-12 1995-01-26 Aharon Eyal A process for the production of water-soluble salts of carboxylic and amino acids

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Title
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