Methods for producing 3-hydroxypropionic acid and other products
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12P-007/40
C12N-009/00
C12N-001/20
C12M-001/00
C12N-015/00
C07H-021/04
C12N-009/02
A61L-015/24
C12P-007/42
C12P-007/52
C12N-015/63
출원번호
US-0498468
(2010-09-27)
등록번호
US-8883464
(2014-11-11)
국제출원번호
PCT/US2010/050436
(2010-09-27)
§371/§102 date
20130212
(20130212)
국제공개번호
WO2011/038364
(2011-03-31)
발명자
/ 주소
Lynch, Michael D.
Gill, Ryan T.
Lipscomb, Tanya E. W.
출원인 / 주소
OPX Biotechnologies, Inc.
대리인 / 주소
Wilson Sonsini Goodrich & Rosati
인용정보
피인용 횟수 :
8인용 특허 :
65
초록
This invention relates to metabolically engineered microorganism strains, such as bacterial strains, in which there is an increased utilization of malonyl-CoA for production of a chemical product, which includes 3-hydroxypropionic acid.
대표청구항▼
1. A method for producing an acrylic acid-based consumer product, said method comprising: i) combining a carbon source, a microorganism, and cell culture to produce 3-hydroxypropionic acid, wherein: a) said cell culture comprises an inhibitor of fatty acid synthase or said microorganism is genetical
1. A method for producing an acrylic acid-based consumer product, said method comprising: i) combining a carbon source, a microorganism, and cell culture to produce 3-hydroxypropionic acid, wherein: a) said cell culture comprises an inhibitor of fatty acid synthase or said microorganism is genetically modified to comprise a deletion of an enzyme, or a substitution of an enzyme with a mutated version of said enzyme, wherein said enzyme selected from the group consisting of: malonyl-CoA-ACP transacylase, beta-ketoacyl-ACP synthase I, beta-ketoacyl-acyl carrier protein synthase II, and enoyl-ACP reductase, thereby providing for reduced conversion of malonyl-CoA to fatty acids; andb) wherein said microorganism is genetically modified for increased enzymatic activity in the microorganism's malonyl-CoA reductase (mcr) pathway by introduction of a heterologous nucleic acid sequence coding for a polypeptide having mono- or bi-functional malonyl-CoA reductase activity;ii) converting said 3-hydroxypropionic acid to acrylic acid; andiii) processing said acrylic acid into a consumer product. 2. The method of claim 1, wherein said carbon source has a ratio of carbon-14 to carbon-12 of about 1.0×10−14 or greater. 3. The method of claim 1, wherein said carbon source is predominantly a sugar selected from the group consisting of: glucose, sucrose, fructose, dextrose, and lactose, or any combination thereof. 4. The method of claim 1, wherein said carbon source is less than 50% glycerol. 5. The method of claim 1, wherein said cell culture comprises an inhibitor of fatty acid synthase. 6. The method of claim 5, wherein said inhibitor of a fatty acid synthase is selected from the group consisting of: thiolactomycin, triclosan, cerulenin, thienodiazaborine, isoniazid, and analogs thereof, or any combination thereof. 7. The method of claim 1, wherein said microorganism is genetically modified for reduced enzymatic activity in the microorganism's fatty acid synthase pathway providing for reduced conversion of malonyl-CoA to fatty acids. 8. The method of claim 7, wherein the reduced enzymatic activity is a reduction in enzymatic activity in an enzyme selected from the group consisting of beta-ketoacyl-ACP reductase, 3-hydroxyacyl-CoA dehydratase, enoyl-ACP reductase, thioesterase, and any combination thereof. 9. The method of claim 7, wherein said microorganism is genetically modified via introduction of a heterologous nucleic acid sequence having an inducible promoter operably linked to a sequence coding for an enzyme in the fatty acid synthase pathway or homolog thereof, or a heterologous nucleic acid sequence coding for an enzyme in the fatty acid synthase pathway or homolog thereof with reduced activity. 10. The method of claim 1, wherein said mutated version of said enzyme is temperature-sensitive. 11. The method of claim 1, wherein said microorganism is genetically modified for increased enzymatic activity in the microorganism's malonyl-CoA reductase (mcr) pathway by introduction of a heterologous nucleic acid sequence coding for a polypeptide having mono-functional malonyl-CoA reductase activity. 12. The method of claim 11, wherein said polypeptide having mono-functional malonyl-CoA reductase activity is NADPH-independent. 13. The method of claim 1, wherein said increase in enzymatic activity in the malonyl-CoA reductase (mcr) pathway occurs by introduction of a heterologous nucleic acid sequence coding for a polypeptide having bi-functional malonyl-CoA reductase enzymatic activity. 14. The method of claim 11, wherein said heterologous nucleic acid sequence is selected from a sequence encoding a polypeptide having at least 90% identity with a sequence selected from SEQ ID NOs. 783-791. 15. The method of claim 1, wherein said 3-hydroxypropionic acid is produced at a specific productivity of greater than 0.05 grams per gram of microorganism cell on a dry weight basis per hour or at a volumetric productivity of greater than 0.5 grams per liter per hour. 16. The method of claim 1, wherein said microorganism is further modified for a trait selected from the group consisting of: increased tolerance to 3-hydroxypropionic acid, increased enzymatic activity in the microorganism's NADPH-dependent transhydrogenase pathway, increased intracellular bicarbonate levels, increased enzymatic activity in the microorganism's acetyl-CoA carboxylase pathway, and combinations thereof. 17. The method of claim 16, wherein said genetically modified microorganism is modified for increased tolerance to 3-hydroxypropionic acid. 18. The method of claim 17, wherein said increased tolerance to 3-hydroxypropionic acid occurs in one or more components of the 3-HP toleragenic complex (3HPTGC), or wherein said increased tolerance to 3-hydroxypropionic acid results from providing at least one genetic modification of each of Group A and Group B of the 3HPTGC. 19. The method of claim 18, wherein said one or more components are selected from the group consisting of: CynS, CynT, AroG, SpeD, SpeE, SpeF, ThrA, Asd, CysM, IroK, IlvA, and homologs thereof, or any combination thereof. 20. The method of claim 18, wherein said genetic modification is a disruption of one or more 3HPTGC repressor genes. 21. The method of claim 20, wherein said one or more 3HPTGC repressor genes are selected from the group consisting of: tyrR, trpR, metJ, purR, lysR, nrdR, and homologs thereof, or any combination thereof. 22. The method of claim 16, wherein said microorganism is further modified for increased enzymatic activity in the microorganism's NADPH-dependent transhydrogenase pathway by introduction of a heterologous nucleic acid sequence coding for a polypeptide having at least 90% identity with one or more sequences selected from the group consisting of SEQ ID NOs. 780 and 782. 23. The method of claim 16, wherein said microorganism is further modified for increased intracellular bicarbonate levels by introduction of a heterologous nucleic acid sequence coding for a polypeptide having cyanase or carbonic anhydrase activity. 24. The method of claim 23, wherein said heterologous nucleic acid sequence is a sequence having at least 90% homology to SEQ ID NO. 337. 25. The method of claim 16, wherein said microorganism is modified for increased enzymatic activity in the microorganism's acetyl-CoA carboxylase pathway by introduction of a heterologous nucleic acid sequence coding for a polypeptide having at least 90% identity with one or more sequences selected from the group consisting of: SEQ ID NOs. 772, 774, 776 and 778. 26. The method of claim 1, wherein said microorganism is further modified to decrease activity of lactate dehydrogenase, phosphate acetyltransferase, pyruvate oxidase, pyruvate-formate lyase, or any combination thereof. 27. The method of claim 1, wherein following (i), said method further comprises extracting 3-hydroxypropionic acid from said cell culture in the presence of a tertiary amine. 28. The method of claim 27, wherein said 3-hydroxypropionic acid is produced at a specific productivity of greater than 0.05 grams per gram of microorganism cell on a dry weight basis per hour or at a volumetric productivity of greater than 0.50 grams per liter per hour. 29. The method of claim 1, wherein said consumer product is selected from the group consisting of diapers, carpet, paint, adhesives, and acrylic glass. 30. The method of claim 29, wherein said consumer product is diapers. 31. The method of claim 1, wherein said heterologous nucleic acid sequence coding for a polypeptide having mono- or bi-functional malonyl-CoA reductase activity is from a species selected from the group consisting of: Chloroflexus aurantiacus, Chloroflexus aggregans, Roseiflexus castenholzii, Roseiflexus sp., Erythrobacter sp., gamma proteobacterium, marine gamma proteobacterium, Sulfolobus tokodaii, and Metallosphaera sedula.
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