Patents Assigned to Fluxome Sciences A/S
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Publication number: 20130209613Abstract: A recombinant micro-organism such as Saccharomyces cerevisiae which produces and excretes into culture medium a stilbenoid metabolite product when grown under stilbenoid production conditions, which expresses in above native levels a ABC transporter which transports said stilbenoid out of said micro-organism cells to the culture medium. The genome of the Saccharomyces cerevisiae produces an auxotrophic phenotype which is compensated by a plasmid which also expresses one or more of said enzymes constituting said metabolic pathway producing said stilbenoid, an expression product of the plasmid is genetically modified to include a ubiquitination tag sequence. Expression of an enzyme participating in catabolism of phenylalanine by the Ehrlich pathway is optionally reduced compared to its native expression level.Type: ApplicationFiled: May 24, 2011Publication date: August 15, 2013Applicant: FLUXOME SCIENCES A/SInventors: Michael Patrik Katz, Thomas Durhuus, Hans Peter Smits, Jochen Forster
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Patent number: 8343739Abstract: A genetically engineered micro-organism having an operative metabolic pathway producing cinnamoyl-CoA and producing pinosylvin therefrom by the action of a stilbene synthase is used for pinosylvin production. Said cinnamic acid may be formed from L-phenylalanine by a L-phenylalanine ammonia lyase (PAL) which is one accepting phenylalanine as a substrate and producing cinammic acid therefrom, preferably such that if the PAL also accepts tyrosine as a substrate and forms coumaric acid therefrom, the ratio Km(phenylalanine)/Km(tyrosine) for said PAL is less than 1:1 and if said micro-organism produces a cinammate-4-hydroxylase enzyme (C4H), the ratio Kcat(PAL)/Kcat(C4H) is at least 2:1.Type: GrantFiled: July 19, 2007Date of Patent: January 1, 2013Assignee: Fluxome Sciences A/SInventors: Michael Katz, Jochen Förster, Helga David, Hans Peter Schmidt, Malin Sendelius, Sara Peterson Bjørn, Thomas Thomasen Durhuus
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Publication number: 20110124067Abstract: A method for the production of a stilbenoid, such as resveratrol or pinosylvin, by fermenting plant material such a grape must using a yeast having a metabolic pathway producing said stilbenoid, separating a solids waste material from said fermentation and extracting said stilbenoid.Type: ApplicationFiled: April 2, 2009Publication date: May 26, 2011Applicant: Fluxome Sciences A/SInventors: Bo Stenhuus, Hans Peter Smits, Thomas Durhuus, Michael Katz
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Publication number: 20110086399Abstract: A cis- or trans-stilbenoid of the general formula (1) in which each of R1, R2, R3, R4 and R5 is hydrogen or hydroxy, or a glycosylated or oligomeric form thereof, such as resveratrol or pinosylvin is produced by cultivating a microorganism such as a genetically engineered yeast to produce said stilbenoid in a culture medium in solid form, and is separated by filtration or settling.Type: ApplicationFiled: April 8, 2009Publication date: April 14, 2011Applicant: FLUXOME SCIENCES A/SInventors: Hans Peter Smits, Helga David, Jochen Forster, Bo Stenhuus
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Publication number: 20100203603Abstract: A cis- or trans-stilbenoid of the general formula (1): in which each of R1, R2, R3, R4 and R5 is hydrogen or hydroxy, or a glycosylated or oligomeric form thereof, is produced by cultivating a micro-organism producing said stilbenoid, in a multi-phase system comprising at least an aqueous first phase containing said micro-organism and a second phase immiscible with said aqueous phase in which (e.g. as which) said stilbenoid accumulates. The second phase may be said stilbenoid or a free or encapsulated solvent compatible with the growth of the micro-organism, for instance an ester.Type: ApplicationFiled: July 25, 2008Publication date: August 12, 2010Applicant: FLUXOME SCIENCES A/SInventors: Hans Peter Schmidt, Michael Katz, Bo Stenhuus, Jochen Förster
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Patent number: 7736884Abstract: The present invention relates to the construction and engineering of cells, more particularly microorganisms for producing PUFAs with four or more double bonds from non-fatty acid substrates through heterologous expression of an oxygen requiring pathway. The invention especially involves improvement of the PUFA content in the host organism through fermentation optimization, e.g. decreasing the temperature and/or designing an optimal medium, or through improving the flux towards fatty acids by metabolic engineering, e.g. through over-expression of fatty acid synthases, over-expression of other enzymes involved in biosynthesis of the precursors for PUFAs, or codon optimization of the heterologous genes, or expression of heterologous enzymes involved in the biosynthesis of the precursor for PUFAs.Type: GrantFiled: June 6, 2005Date of Patent: June 15, 2010Assignee: Fluxome Sciences A/SInventors: Nina Katarina Gunnarsson, Jochen Forster, Jens Bredal Nielsen
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Publication number: 20090317881Abstract: A genetically engineered micro-organism having an operative metabolic pathway producing cinnamoyl-CoA and producing pinosylvin therefrom by the action of a stilbene synthase is used for pinosylvin production. Said cinnamic acid may be formed from L-phenylalanine by a L-phenylalanine ammonia lyase (PAL) which is one accepting phenylalanine as a substrate and producing cinammic acid therefrom, preferably such that if the PAL also accepts tyrosine as a substrate and forms coumaric acid therefrom, the ratio Km(phenylalanine)/Km(tyrosine) for said PAL is less than 1:1 and if said micro-organism produces a cinammate-4-hydroxylase enzyme (C4H), the ratio Kcat(PAL)/Kcat(C4H) is at least 2:1.Type: ApplicationFiled: July 19, 2007Publication date: December 24, 2009Applicant: FLUXOME SCIENCES A/SInventors: Michael Katz, Jochen Förster, Helga David, Hans Peter Schmidt, Malin Sendelius, Sara Peterson Bjørn, Thomas Thomasen Durhuus
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Publication number: 20090035839Abstract: A recombinant micro-organism producing resveratrol by a pathway in which phenylalanine ammonia lyase (PAL) produces trans-cinnamic acid from phenylalanine, cinnamate 4-hydroxylase (C4H) produces 4-coumaric acid from said trans-cinnamic acid, 4-coumarate-CoA ligase (4CL) produces 4-coumaroyl CoA from said 4-coumaric acid, and resveratrol synthase (VST) produces said resveratrol from said 4-coumaroyl CoA, or in which L-phenylalanine- or tyrosine-ammonia lyase (PAL/TAL) produces 4-coumaric acid, 4-coumarate-CoA ligase (4CL) produces 4-coumaroyl CoA from said 4-coumaric acid, and resveratrol synthase (VST) produces said resveratrol from said 4-coumaroyl CoA. The micro-organism may be a yeast, fungus or bacterium including Saccharomyces cerevisiae, E. coli, Lactococcus lactis, Aspergillus niger, or Aspergillus oryzae.Type: ApplicationFiled: April 17, 2008Publication date: February 5, 2009Applicant: Fluxome Sciences A/SInventors: Michael Katz, Hans Peter Smits, Jochen Forster, Jens Bredal Nielsen
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Publication number: 20080286844Abstract: A recombinant micro-organism producing resveratrol by a pathway in which phenylalanine ammonia lyase (PAL) produces trans-cinnamic acid from phenylalanine, cinnamate 4-hydroxylase (C4H) produces 4-coumaric acid from said trans-cinnamic acid, 4-coumarate-CoA ligase (4CL) produces 4-coumaroyl CoA from said 4-coumaric acid, and resveratrol synthase (VST) produces said resveratrol from said 4-coumaroyl CoA, or in which L-phenylalanine- or tyrosine-ammonia lyase (PAL/TAL) produces 4-coumaric acid, 4-coumarate-CoA ligase (4CL) produces 4-coumaroyl CoA from said 4-coumaric acid, and resveratrol synthase (VST) produces said resveratrol from said 4-coumaroyl CoA. The micro-organism may be a yeast, fungus or bacterium including Saccharomyces cerevisiae, E. coli, Lactococcus lactis, Aspergillus niger, or Aspergillus oryzae.Type: ApplicationFiled: February 21, 2006Publication date: November 20, 2008Applicant: FLUXOME SCIENCES A/SInventors: Michael Katz, Hans Peter Smits, Jochen Forster, Jens Bredal Nielsen
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Patent number: 7393669Abstract: A recombinant prototrophic micro-organism such as a yeast is provided which over-expresses the activity of an enzyme catalysing the conversion of glucose-1 phosphate to glucose-6 phosphate in the galactose uptake and metabolism pathway. Suitably the increased enzyme activity is due to over-expression of the gene PGM2. This produces increased uptake of galactose and increased ethanol production when the organism is grown on a galactose containing medium.Type: GrantFiled: July 7, 2003Date of Patent: July 1, 2008Assignee: Fluxome Sciences A/SInventors: Christoffer Bro, Birgitte Regenberg, Jens Nielsen
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Publication number: 20060257983Abstract: A metabolically engineered micro-organism has an operative first metabolic pathway in which a first metabolite is transformed into a second metabolite in a reaction in which NAD is a cofactor for a first enzyme, suitably a phosphorylating dehydrogenase, said reaction step producing NADH. Said second metabolite is transformed into at least one further metabolite in a reaction catalysed by a second enzyme, suitably a kinase. The organism has an operative second metabolic pathway characterised by an enzyme activity in excess of a native level in respect of a third enzyme, suitably a non-phosphorylating dehydrogenase, e.g. GAPN, catalysing a non-reversible reaction in which NADP is a cofactor and NADPH is a product. Said first metabolite is transformed into a said further metabolite without the involvement of said second enzyme.Type: ApplicationFiled: November 25, 2003Publication date: November 16, 2006Applicant: Fluxome Sciences A/SInventors: Christoffer Bro, Brigitte Regenberg, Jens Nielsen
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Patent number: 7018829Abstract: A recombinant microbial cell comprises at least one increased expressible enzyme activity controlling anabolic metabolism of ammonia as a nutrient source, the increased enzyme activity being an NADH-dependent activity catalysing the reaction (a) 2-oxoglutarate+NH3+NADH?glutamate+NAD or being an activity catalysing the reaction (b) 2-oxoglutarate+glutamine+NADH?2 glutamate+NAD or being an activity catalysing the reaction (c) glutamate+NH3+ATP?glutamine+ADP+Pi. The increased enzyme activity is encoded by a nucleic acid coding sequence linked to an expression signal not natively associated with the nucleic acid coding sequence and is increased as compared to the expression of the enzyme activity when the nucleic acid coding sequence is associated with its native expression signal.Type: GrantFiled: July 12, 1999Date of Patent: March 28, 2006Assignee: Fluxome Sciences A/SInventors: Jens Nielsen, Torben Lauesgaard Nissen, Morten C. Kielland-Brandt
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Publication number: 20050009135Abstract: A recombinant prototrophic micro-organism such as a yeast is provided which over-expresses the activity of an enzyme catalysing the conversion of glucose-1 phosphate to glucose-6 phosphate in the galactose uptake and metabolism pathway. Suitably the increased enzyme activity is due to over-expression of the gene PGM2. This produces increased uptake of galactose and increased ethanol production when the organism is grown on a galactose containing medium.Type: ApplicationFiled: July 7, 2003Publication date: January 13, 2005Applicant: FLUXOME SCIENCES A/SInventors: Christoffer Bro, Birgitte Regenberg, Jens Nielsen