WO1993012219A1 - Controlling growth of filamentous microorganisms - Google Patents
Controlling growth of filamentous microorganisms Download PDFInfo
- Publication number
- WO1993012219A1 WO1993012219A1 PCT/GB1991/002234 GB9102234W WO9312219A1 WO 1993012219 A1 WO1993012219 A1 WO 1993012219A1 GB 9102234 W GB9102234 W GB 9102234W WO 9312219 A1 WO9312219 A1 WO 9312219A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- nutrient
- culture
- limiting
- source
- carbon
- Prior art date
Links
- 244000005700 microbiome Species 0.000 title claims abstract description 38
- 235000015097 nutrients Nutrition 0.000 claims abstract description 113
- 238000000034 method Methods 0.000 claims abstract description 40
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 22
- 239000001963 growth medium Substances 0.000 claims abstract description 10
- 230000003111 delayed effect Effects 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 10
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 10
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 8
- 238000010790 dilution Methods 0.000 claims description 8
- 239000012895 dilution Substances 0.000 claims description 8
- 239000011777 magnesium Substances 0.000 claims description 8
- 229910052749 magnesium Inorganic materials 0.000 claims description 8
- 230000003247 decreasing effect Effects 0.000 claims description 6
- 239000002207 metabolite Substances 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 5
- 239000010452 phosphate Substances 0.000 claims description 5
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 claims description 3
- 241000223218 Fusarium Species 0.000 claims description 3
- 238000011084 recovery Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 239000002609 medium Substances 0.000 description 9
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
- 238000000855 fermentation Methods 0.000 description 7
- 230000004151 fermentation Effects 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 241000223195 Fusarium graminearum Species 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 4
- 229930091371 Fructose Natural products 0.000 description 3
- 239000005715 Fructose Substances 0.000 description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 238000012366 Fed-batch cultivation Methods 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000228150 Penicillium chrysogenum Species 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000187432 Streptomyces coelicolor Species 0.000 description 1
- 241001655322 Streptomycetales Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000020588 necrotizing soft tissue infection Diseases 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010572 single replacement reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/14—Fungi; Culture media therefor
Definitions
- This invention relates to a process for the continuous or fed batch cultivation of a filamentous microorganism which is controlled to delay or prevent the development of an undesirable variant in the the culture.
- the invention relates to a process for the production of a proteinaceous product or a metabolite.
- filamentous microorganisms particularly fermentations for the production of proteinaceous compositions where it is often desirable to produce filamentous microorganisms having only limited hyphal branching.
- cultivation of a filamentous microorganism can be controlled to delay or prevent the development of an undesirable variant in the culture.
- microorganism in a culture medium to which are supplied sources of appropriate nutrients including carbon are nutrient source being supplied in an amount limiting to the growth of the culture and constituting a limiting nutrient thereto, wherein development of an unwanted variant of the filamentous microorganism is restricted and/or declared by supplying a first nutrient source to the culture as a limiting nutrient and then changing the nutrients supply to the culture in a manner such that a second nutrient source replaces the first nutrient source as the limiting nutrient.
- a filamentous microorganism in a culture medium to which are supplied sources of other appropriate nutrients including carbon.
- One nutrient source being supplied in an amount limiting to the growth of the culture and constituting a limiting nutrient thereto, and separation of the filamentous microrganism from the culture wherein development of an unwanted variant of the filamentous microorganism is restricted and/or delayed by supplying a first nutrient source to the culture as a limiting nutrient and then changing nutrients supply to the culture in a manner such that a second nutrient source replaces the first nutrient source as the limiting nutrient.
- a process for the production of a metabolite by cultivation in continuous or fed batch culture of a filamentous microorganism in a culture medium to which are supplied sources of carbon and other appropriate nutrients, the carbon or another nutrient source being supplied in an amount limiting to the growth of the culture and constituting a limiting nutrient there to, and recovery of the metabolite from the filamentous microorganism produced or from the culture medium wherein development of a variant of the filamentous microorganism is restricted and/or delayed by supplying a first nutrient source to the culture as a limiting nutrient and then changing the nutrients supply to the culture in a manner such that a second nutrient source replaces the first nutrient source as the limiting nutrient.
- filamentous microorganism may be used to produce a proteinaceous product by the fermentation process described in GB 1346061; GB 1346062 and EP 123434.
- Any suitable filamentous microorganism may be cultivated to produce the proteinaceous product, for example strains of the genus Fusarium such as Fusarium graminearum (Schwabe) which is deposited at the Commonwealth Mycological Institute, Kew, under numbers IMI 145425 and CMI CC No 346,762 and strains of Penicillium notatum
- the invention may also be employed in a fermentation process using for example a streptomycete for example Streptomyces coelicolor to produce a metabolite, for example an antibiotic which may be streptomycin.
- the limiting nutrients are suitably chosen according to the fermentation and the
- a single replacement of limiting nutrient may be employed but preferably the process is conducted with a series of replacements of limiting nutrient at intervals throughout its period of
- the replacements may involve only two nutrient sources as limiting nutrients but preferably the process is conducted with three or more different nutrient sources being used in turn as the limiting nutrient. Preferably the process is operated with a series of three or more nutrient sources being used as limiting nutrient according to a regular cycle.
- the timing of the replacement of one nutrient source by another as limiting nutrient can be chosen in a variety of ways.
- the growth of the culture can be monitored and one nutrient source can be replaced by another when the variant whose development is to be controlled has developed to a predetermined extent, eg when it forms at for example 1% of the microorganism cells present in the culture.
- Suitable nutrient sources for use as limiting nutrient include sources of carbon, for example xylose, maltose, ribose, fructose, sucrose or glucose, magnesium, phosphate and sulphate, and especially if a non nitrogen containing metabolite is to be produced, of nitrogen.
- the nutrient source used as the limiting nutrient in any cycle of replacements is not a nutrient which is of primary importance in producing the product of the process such as the nitrogen source in a process for producing a proteinaceous product.
- Strategies involving changing the carbon source as the growth limiting nutrient may be adopted especially between glucose and fructose.
- Suitable strategies for altering the limiting nutrient include the following, designed primarily for use in a process for the production of a proteinaceous product by cultivation of a Fusarium strain:- a) a strategy in which the culture is regularly monitored and the limiting nutrient is altered when there is an indication that the microorganism population in the culture has begun to alter unfavourably due to the formation of an undesirable variant.
- three different nutrient sources may be used alternatively as the limiting nutrient as follows:- 1.
- Carbon source eg glucose
- a preferred strategy for general use in the process of the invention is to alter the nutrient limitation at regular 7 day intervals starting with an initially carbon limited chemostat.
- the cycle is suitably as follows:- 1. Carbon source
- a cycle of limiting nutrients repeated throughout the process is a preferred strategy in many instances. It is preferred that the proposed limiting nutrients is not important for the production of the product of the process. It would not for example be a preferred strategy for the production of an antibiotic which sequences sulphate in its synthesis to use sulphate as a limiting nutrient.
- the dilution rate is suitably decreased, eg by an amount in the range 0.05 to 0.10 hr -1 , in order to remove any undesirable variant from the microorganism population more effectively.
- Figure 1 shows the CCI-1 variant which was first detected after ⁇ 100 generations arising spontaneously in an A 3/5 continuous culture during a glucose-limited fermentation of A 3/5. After a further 100 generations approximately, CCI-1 made up > 90% of the total population.
- FIG. 2 shows that CCI-1 had a selection coefficient (S) of -0.039 generation under magnesium-limitation.
- Figure 3 shows CCI-1 remained approximately constant when grown in ammonia-limited culture.
- Figure 4 shows CCI-1 remained approximately constant when grown in sulphate-limited chemostat culture.
- D 0.16h -1
- Figure 6 shows how CCI-1 takeover can be prevented.
- the culture is under glucose-limitation and CCI-1 begins to supplant the wildtype.
- the culture was switched to magnesium-limitation and the increase in CCI-1 was halted.
- the dotted line shows predicted increase of CCI-1 if glucose-limitation had been maintained.
- compositions of the relevant Vogels media used are shown in the Table below.
- CCI-1 can be controlled and in some cases reduced by sulphate or magnesium limitation conditions and stabilised under nitrogen limitation conditions. This indicates that by monitoring the variants present and altering the growth limitation conditions appropriately when their population is low it is possible to delay the need to close a manufacturing process down because unwanted organisms have overwhelmed the wanted organisms.
- Apparatus A commercially available continuous fermenter with air and nutrient feed facilities sold by Braun under the trade name Biostat M. (2 litre)
- antifoam 0.25% (v/v) polypropylene glycol (mixed molecular weight)
- stirrer speed 1400 rpm
- biomass approximately 2g dry weight 1 culture medium (for all limitations).
- Assessment of population composition composition of the population was assessed by making viable counts on agar solidified Vogel's medium. Samples from the fermenter were diluted in sterile distilled water and 0.1 ml of the suspension were spread on 10-15 agar plates to yield 20-60 colonies per plate. Colony forming units (derived from either mycelial fragments or spores) were counted after 72h incubation at 25°C. Colonial mutant colonies could be distinguished from wild-type colonies because they formed dense colonies which increased slowly in diameter and they were counted separately from the wild-type colonies. Viable counts were made at approximately 24 or 48 h intervals.
- Limiting nutrient stock solutions were prepared as shown in the table. These were limited in one particular nutrient. When switching to a different limiting nutrient a 1-48 hr time interval was required for the levels of the particular nutrient to be reduced as desired in the fermenter vessel, as the nutrient would have been in excess under the previous set of conditions.
- This procedure keeps the colonial mutant population at below critical levels for a prolonged period.
- a) is the preferable strategy, but if the process precludes several types of limitation (such as not limiting the nitrogen source in a process producing protein, as not limiting for sulphate in the production of an antibiotic which requires sulphate in its synthesis) then it may be necessary to follow the type of strategy suggested in b).
- Microorganism Fusarium graminearum IMI CC Number: 346762
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Botany (AREA)
- Mycology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK92900581T DK0620846T3 (en) | 1991-12-16 | 1991-12-16 | Controlling the growth of filamentous microorganisms |
EP92900581A EP0620846B1 (en) | 1991-12-16 | 1991-12-16 | Controlling growth of filamentous microorganisms |
AU90740/91A AU669651B2 (en) | 1991-12-16 | 1991-12-16 | Controlling growth of filamentous microorganisms |
CA002125648A CA2125648C (en) | 1991-12-16 | 1991-12-16 | Controlling growth of filamentous microorganisms |
ES92900581T ES2113937T3 (en) | 1991-12-16 | 1991-12-16 | CONTROLLING THE GROWTH OF FILAMENTAL MICROORGANISMS. |
PCT/GB1991/002234 WO1993012219A1 (en) | 1990-12-12 | 1991-12-16 | Controlling growth of filamentous microorganisms |
DE69129042T DE69129042T2 (en) | 1991-12-16 | 1991-12-16 | GROWTH CONTROL OF THREADED MICROORGANISMS. |
US08/244,859 US5563065A (en) | 1990-12-12 | 1991-12-16 | Controlling growth of filamentous microorganisms |
JP4501736A JPH07504560A (en) | 1991-12-16 | 1991-12-16 | Growth control of filamentous microorganisms |
GR980400268T GR3026278T3 (en) | 1991-12-16 | 1998-03-05 | Controlling growth of filamentous microorganisms. |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB909027016A GB9027016D0 (en) | 1990-12-12 | 1990-12-12 | Controlling growth of filamentous microorganisms |
CA002125648A CA2125648C (en) | 1991-12-16 | 1991-12-16 | Controlling growth of filamentous microorganisms |
PCT/GB1991/002234 WO1993012219A1 (en) | 1990-12-12 | 1991-12-16 | Controlling growth of filamentous microorganisms |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1993012219A1 true WO1993012219A1 (en) | 1993-06-24 |
Family
ID=27169792
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1991/002234 WO1993012219A1 (en) | 1990-12-12 | 1991-12-16 | Controlling growth of filamentous microorganisms |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO1993012219A1 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995021910A1 (en) * | 1994-02-10 | 1995-08-17 | Zeneca Limited | Modification of filamentous microorganisms |
US5641426A (en) * | 1994-04-29 | 1997-06-24 | Minnesota Mining And Manufacturing Company | Light modulating device having a vinyl ether-based matrix |
GB2348649A (en) * | 1999-03-17 | 2000-10-11 | Biodiversity Ltd | Biochemical synthesis apparatus |
GB2518725A (en) * | 2013-07-24 | 2015-04-01 | Marlow Foods Ltd | Edible fungi |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4400467A (en) * | 1980-07-14 | 1983-08-23 | Standard Oil Company (Indiana) | Process of using xanthomonas campestris NRRL B-12075 and NRRL B-12074 for making heteropolysaccharide |
-
1991
- 1991-12-16 WO PCT/GB1991/002234 patent/WO1993012219A1/en active IP Right Grant
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4400467A (en) * | 1980-07-14 | 1983-08-23 | Standard Oil Company (Indiana) | Process of using xanthomonas campestris NRRL B-12075 and NRRL B-12074 for making heteropolysaccharide |
Non-Patent Citations (2)
Title |
---|
MICROBIOLOGY ABSTRACTS A. INDUSTRIAL AND APPLIED MICROBIOLOGY. vol. 11, no. 11, November 1976, LONDON GB page 1; KURBACKAJA Z.A. ET AL.: 'Effect of different ratios of carbon and nitrogen concentration in medium on growth and toxin-formation in Aspergillus fumigatus Fres.' Abstract N. 11a7582 * |
TRANSACTIONS OF THE BRITISH MYCOLOGICAL SOCIETY vol. 87, no. 2, September 1986, CAMBRIDGE GB pages 215 - 222; JEANNE M.M. INCH ET AL.: 'Growth and blastopore formation by Paelomyces fumosoroseus, a pathogen of brown planthopper (Nilaparvata lugens)' * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995021910A1 (en) * | 1994-02-10 | 1995-08-17 | Zeneca Limited | Modification of filamentous microorganisms |
US5935841A (en) * | 1994-02-10 | 1999-08-10 | Zeneca Limited | Microbiological process |
US5641426A (en) * | 1994-04-29 | 1997-06-24 | Minnesota Mining And Manufacturing Company | Light modulating device having a vinyl ether-based matrix |
GB2348649A (en) * | 1999-03-17 | 2000-10-11 | Biodiversity Ltd | Biochemical synthesis apparatus |
GB2348649B (en) * | 1999-03-17 | 2004-07-07 | Biodiversity Ltd | A method for producing a biochemical from microorganisms and apparatus therefor |
GB2518725A (en) * | 2013-07-24 | 2015-04-01 | Marlow Foods Ltd | Edible fungi |
GB2518725B (en) * | 2013-07-24 | 2020-04-15 | Marlow Foods Ltd | Edible fungi |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Toyosaki et al. | Screening of bacterial cellulose-producing Acetobacter strains suitable for agitated culture | |
US6132999A (en) | L-threonine-producing microbacteria and a method for the production of L-threonine | |
EP0194760B1 (en) | Xylose isomerase, a method for production of such xylose isomerase, immobilized xylose isomerase and a method for isomerization of glucose to fructose | |
US5096819A (en) | Hyperproduction of poly-β-hydroxybutyrate during exponential growth by mutant strains of Azotobacter vinelandii | |
Gwinn et al. | Transformation of Bacillus licheniformis | |
WO1993012219A1 (en) | Controlling growth of filamentous microorganisms | |
AU669651B2 (en) | Controlling growth of filamentous microorganisms | |
US5563065A (en) | Controlling growth of filamentous microorganisms | |
EP0530260B1 (en) | Production of a proteinaceous composition | |
JPS58158185A (en) | Breeding of amino acid-producing bacteria having improved rate of growth | |
US5935841A (en) | Microbiological process | |
EP0482908B1 (en) | Process for producing streptovaricin | |
Miyoshi et al. | BIOSYNTHESIS OF BICYCLOMYCIN I. APPEARANCE OF AERIAL MYCELIA NEGATIVE STRAINS (am-) | |
Bok et al. | Selective isolation of acidophilic Streptomyces strains for glucose isomerase production | |
JPS6257316B2 (en) | ||
Bacon et al. | SPONTANEOUS AND MUTATOR-INDUCED REVERSIONS OF AN ESCHERICHIA COLI AUXOTROPH I: Prototrophic Types and Their Growth Characteristics | |
US5137825A (en) | Process for producing streptovaricin | |
JP3239903B2 (en) | Creation of new L-threonine-producing bacteria by Escherichia coli and method for producing L-threonine thereby | |
US5922581A (en) | Process for the production of d-biotin | |
Macdonald | Storage of conidia of Penicillium chrysogenum in liquid nitrogen | |
JPH05244973A (en) | Actinomadura fibrosa sp. nov. nrrl18348 and production of polyether-based antibiotic from this strain | |
KR960007613B1 (en) | Method for producing el-glutamic acid using microorganisms | |
Van de Vondervoort et al. | Isolation of a fluffy mutant of Aspergillus niger from chemostat culture and its potential use as a morphologically stable host for protein production | |
SON et al. | Studies on microbial penicillin amidase (IV) the production of penicillin amidase from a partially constitutive mutant of Bacillus megaterium | |
KR900007945B1 (en) | Novel microorganism for producing of glutamic acid |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AT AU BB BG BR CA CH CS DE DK ES FI GB HU JP KP KR LK LU MG MN MW NL NO PL RO SD SE SU US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LU MC NL SE BF BJ CF CG CI CM GA GN ML MR SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 1992900581 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2125648 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 08244859 Country of ref document: US |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 1992900581 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 1992900581 Country of ref document: EP |