Microorganisms and methods for production of 4-hydroxybutyrate, 1,4-butanediol and related compounds
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12N-001/20
C12P-007/42
C12N-015/63
C12P-007/18
C12N-009/18
C12N-015/52
C07C-031/20
C07C-059/01
C08G-018/28
C08G-018/32
C08G-063/06
C08G-063/16
C08G-063/181
C08G-069/02
출원번호
US-0908907
(2013-06-03)
등록번호
US-9677045
(2017-06-13)
발명자
/ 주소
Pharkya, Priti
Burgard, Anthony P.
Van Dien, Stephen J.
Osterhout, Robin E.
Burk, Mark J.
Trawick, John D.
Kuchinskas, Michael P.
Steer, Brian
출원인 / 주소
Genomatica, Inc.
대리인 / 주소
Jones Day
인용정보
피인용 횟수 :
0인용 특허 :
97
초록▼
The invention provides non-naturally occurring microbial organisms having a 4-hydroxybutyrate pathway and being capable of producing 4-hydroxybutyrate, wherein the microbial organism comprises one or more genetic modifications. The invention additionally provides methods of producing 4-hydroxybutyra
The invention provides non-naturally occurring microbial organisms having a 4-hydroxybutyrate pathway and being capable of producing 4-hydroxybutyrate, wherein the microbial organism comprises one or more genetic modifications. The invention additionally provides methods of producing 4-hydroxybutyrate or related products using the microbial organisms.
대표청구항▼
1. A non-naturally occurring microbial organism, said microbial organism having a 4-hydroxybutyrate pathway and being capable of producing 4-hydroxybutyrate, wherein said microbial organism comprises genetic modifications, said genetic modifications comprising: (A) a genetic modification that increa
1. A non-naturally occurring microbial organism, said microbial organism having a 4-hydroxybutyrate pathway and being capable of producing 4-hydroxybutyrate, wherein said microbial organism comprises genetic modifications, said genetic modifications comprising: (A) a genetic modification that increases expression of phosphoenolpyruvate carboxylase;(B) a genetic modification that increases expression of alpha-ketoglutarate dehydrogenase; and(C) a genetic modification that decreases expression of an acyl coenzyme A thioesterase. 2. The microbial organism of claim 1, wherein: (K) the microbial organism has decreased production of ethanol, acetate, pyruvate or alanine, or a combination thereof, relative to a parent microbial organism in the absence of said genetic modification;(L) the microbial organism has decreased production of glutamate relative to a parent microbial organism in the absence of said genetic modification; and(M) the microbial organism has decreased production of gamma-butyrolactone relative to a parent microbial organism in the absence of said genetic modification. 3. The microbial organism of claim 1, wherein said microbial organism further comprises a 4-hydroxybutyryl-CoA pathway. 4. A method for producing 4-hydroxybutyrate, comprising culturing the non-naturally occurring microbial organism of claim 1 under conditions and for a sufficient period of time to produce 4-hydroxybutyrate. 5. The method of claim 4, wherein: (K) the microbial organism has decreased production of ethanol, acetate, pyruvate or alanine, or a combination thereof, relative to a parent microbial organism in the absence of said genetic modification;(L) the microbial organism has decreased production of glutamate relative to a parent microbial organism in the absence of said genetic modification; and(M) the microbial organism has decreased production of gamma-butyrolactone relative to a parent microbial organism in the absence of said genetic modification. 6. The method of claim 4, wherein said non-naturally occurring microbial organism is in a substantially anaerobic culture medium. 7. The microbial organism of claim 1, wherein said microbial organism further comprises a genetic modification selected from: (D) a genetic modification that increases expression of a non-phosphotransferase (PTS) glucose uptake system;(E) a genetic modification that increases expression of a gamma-butyrolactone esterase;(F) a genetic modification that decreases expression of succinyl-CoA synthetase;(G) a genetic modification that decreases expression of an alcohol dehydrogenase(H) a genetic modification that decreases expression of a non-energy-producing NADH dehydrogenase;(I) a genetic modification that decreases expression of a cytochrome oxidase; and(J) a combination of two or more of the genetic modifications of parts (C)-(I). 8. The microbial organism of claim 7, wherein: (N) the microbial organism of part (D) has a genetic modification comprising increased expression of a permease, glucokinase, or a glucose facilitator, or a combination thereof;(O) the microbial organism of part (E) has decreased production of gamma-butyrolactone relative to a parent microbial organism in the absence of said genetic modification;(P) the microbial organism of part (F) has increased production of 4-hydroxybutyrate relative to a parent microbial organism in the absence of said genetic modification;(Q) the microbial organism of part (G) has decreased backflux from a downstream product of the 4-hydroxybutyrate pathway relative to a parent microbial organism in the absence of said genetic modification;(R) the microbial organism of part (H) has suppressed depletion of the NADH pool or increased energy efficiency in the microbial organism, or a combination thereof, relative to a parent microbial organism in the absence of said genetic modification;(S) the microbial organism of part (I) has increased energy efficiency relative to a parent microbial organism in the absence of said genetic modification; or(T) the microbial organism of part (I) has increased tolerance to a range of oxygen concentrations relative to a parent microbial organism in the absence of said genetic modification. 9. The method of claim 4, wherein said microbial organism further comprises a genetic modification selected from: (C) a genetic modification that increases expression of a non-phosphotransferase (PTS) glucose uptake system;(D) a genetic modification that increases expression of a gamma-butyrolactone esterase;(E) a genetic modification that decreases expression of succinyl-CoA synthetase;(F) a genetic modification that decreases expression of an alcohol dehydrogenase(G) a genetic modification that decreases expression of a non-energy-producing NADH dehydrogenase;(H) a genetic modification that decreases expression of a cytochrome oxidase; and(I) a combination of two or more of the genetic modifications of parts (C)-(I). 10. The method of claim 9, wherein: (N) the microbial organism of part (C) has a genetic modification comprising increased expression of a permease, glucokinase, or a glucose facilitator, or a combination thereof;(O) the microbial organism of part (D) has decreased production of gamma-butyrolactone relative to a parent microbial organism in the absence of said genetic modification;(P) the microbial organism of part (E) has increased production of 4-hydroxybutyrate relative to a parent microbial organism in the absence of said genetic modification;(Q) the microbial organism of part (F) has decreased backflux from a downstream product of the 4-hydroxybutyrate pathway relative to a parent microbial organism in the absence of said genetic modification;(R) the microbial organism of part (G) has suppressed depletion of the NADH pool or increased energy efficiency in the microbial organism, or a combination thereof, relative to a parent microbial organism in the absence of said genetic modification;(S) the microbial organism of part (H) has increased energy efficiency relative to a parent microbial organism in the absence of said genetic modification; or(T) the microbial organism of part (H) has increased tolerance to a range of oxygen concentrations relative to a parent microbial organism in the absence of said genetic modification. 11. The microbial organism of claim 1, wherein the microbial organism has a genetic modification comprising at least two genetic modifications that decrease expression of at least two acyl coenzyme A thioesterases. 12. The method of claim 4, wherein the microbial organism has a genetic modification comprising at least two genetic modifications that decrease expression of at least two acyl coenzyme A thioesterases.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (97)
Gokarn,Ravi R.; Selifonova,Olga V.; Jessen,Holly Jean; Gort,Steven John; Selmer,Thorsten; Buckel,Wolfgang, 3-Hydroxypropionic acid and other organic compounds.
Huisman Gjalt W. ; Skraly Frank ; Martin David P. ; Peoples Oliver P., Biological systems for manufacture of polyhydroxyalkanoate polymers containing 4-hydroxyacids.
Huisman, Gjalt W.; Skraly, Frank; Martin, David P.; Peoples, Oliver P., Biological systems for manufacture of polyhydroxyalkanoate polymers containing 4-hydroxyacids.
Tobin Allan J. (Los Angeles CA) Erlander Mark G. (Tarzana CA) Kaufman Daniel L. (Santa Monica CA) Clare-Salzler Michael J. (Los Angeles CA), Cloned glutamic acid decarboxylase peptides.
Burdette Douglas S. ; Zeikus Joseph G., Cloning and expression of the gene encoding thermoanaerobacter ethanolicus 39E secondary-alcohol dehydrogenase and enzy.
Burk, Mark J.; Van Dien, Stephen J.; Burgard, Anthony P.; Niu, Wei, Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors.
Frommer Wolf-Bernd (Berlin DEX) Riesmeier Jorg (Berlin DEX), DNA sequences with oligosaccharide transporter, plasmids, bacteria and plants containing a transporter as well as a proc.
Davis,S. Christopher; Grate,John H.; Gray,David R.; Gruber,John M.; Huisman,Gjalt W.; Ma,Steven K.; Newman,Lisa M.; Sheldon,Roger; Wang,Li A, Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives.
Davis,S. Christopher; Grate,John H.; Gray,David R.; Gruber,John M.; Huisman,Gjalt W.; Ma,Steven K.; Newman,Lisa M.; Sheldon,Roger; Wang,Li A, Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives and vicinal cyano, hydroxy substituted carboxylic acid esters.
Cao,Yongwei; Hinkle,Gregory J.; Slater,Steven C.; Chen,Xianfeng; Goldman,Barry S., Expression of microbial proteins in plants for production of plants with improved properties.
Rieping, Mechthild; Bastuck, Christine; Hermann, Thomas; Thierbach, Georg, Fermentation process for the preparation of L-amino acids using strains of the family Enterobacteriaceae.
Tobin Allan J. ; Erlander Mark G. ; Kaufman Daniel L., Hybridomas and monoclonal antibodies that specifically bind to glutamic acid decarboxylase peptides.
Broecker Franz Josef (Ludwigshafen DT) Schwarzmann Matthias (Limburgerhof DT), Manufacture of butanediol and/or tetrahydrofuran from maleic and/or succinic anhydride via g
상세보기
Tobin Allan J. ; Erlander Mark G. ; Kaufman Daniel L., Method for ameliorating glutamic acid decarboxylase associated autoimmune disorders.
Donnelly Mark I. ; Sanville-Millard Cynthia ; Chatterjee Ranjini, Method for construction of bacterial strains with increased succinic acid production.
Allan J. Tobin ; Mark G. Erlander ; Daniel L. Kaufman, Methods and kits useful for determining the status of and detecting pancreatic B-cell associated autoimmune diseases.
Gruys Kenneth James ; Mitsky Timothy Albert ; Kishore Ganesh Murthy ; Slater Steven Charles ; Padgette Stephen Rogers ; Stark David Martin, Methods of optimizing substrate pools and biosynthesis of poly-.beta.-hydroxybutyrate-co-poly-.beta.-hydroxyvalerate in.
Gruys Kenneth James ; Mitsky Timothy Albert ; Kishore Ganesh Murthy ; Slater Steven Charles ; Padgette Stephen Rogers ; Stark David Martin, Methods of optimizing substrate pools and biosynthesis of poly-.beta.-hydroxybutyrate-co-poly-.beta.-hydroxyvalerate in.
Van Dien, Stephen J.; Burgard, Anthony P.; Haselbeck, Robert; Pujol-Baxley, Catherine J.; Niu, Wei; Trawick, John D.; Yim, Harry; Burk, Mark J.; Osterhout, Robin E.; Sun, Jun, Microorganisms for the production of 1,4-butanediol and related methods.
Timothy A. Mitsky ; Steven C. Slater ; Steven E. Reiser ; Ming Hao ; Kathryn L. Houmiel, Multigene expression vectors for the biosynthesis of products via multienzyme biological pathways.
Steinbuchel Alexander,DEX ; Liebergesell Mathias,DEX ; Valentin Henry ; Pries Andreas,DEX, PHA E and PHA C components of poly(hydroxy fatty acid) synthase from thiocapsa pfennigii.
Tobin Allan J. (Los Angeles CA) Erlander Mark G. (Tarzana CA) Kaufman Daniel L. (Santa Monica CA) Clare-Salzler Michael J. (Gainesville FL), Peptides derived from glutamic acid decarboxylase.
Cannon, Maura; Cannon, Francis C.; McCool, Gabriel J.; Valentin, Henry E.; Gruys, Kenneth J., Polyhydroxyalkanoate biosynthesis associated proteins and coding region in bacillus megaterium.
Matsuyama Akinobu (Niigata JPX) Nikaido Teruyuki (Niigata JPX) Kobayashi Yoshinori (Niigata JPX), Process for producing optically active 1,3-butanediol by reduction of 4-hydroxy-2-butanone.
Emptage,Mark; Haynie,Sharon L.; Laffend,Lisa A.; Pucci,Jeff P.; Whited,Gregory, Process for the biological production of 1,3-propanediol with high titer.
Emptage,Mark; Haynie,Sharon L.; Laffend,Lisa A.; Pucci,Jeff P.; Whited,Gregory Marshall, Process for the biological production of 1,3-propanediol with high titer.
Gottschalk G. (Nrtenhardenberg DEX) Averhoff Beate (Gottingen DEX), Process for the microbiological preparation of 1,3-propane-diol from glycerol by citrobacter.
Rieping,Mechthild; Hermann,Thomas, Process for the production of L-amino acids using strains of the family Enterobacteriaceae that contain an attenuated fruR gene.
Somerville Christopher R. (Portola Valley CA) Nawrath Christiane (Palo Alto CA) Poirier Yves (Palo Alto CA), Processes for producing polyhydroxybutyrate and related polyhydroxyalkanoates in the plastids of higher plants.
Jao Go Pan KR; Soo An Shin KR; Chan Kyu Park KR; Pil Kim KR; Dong Eun Chang KR; Jae Eun Kim KR, Pta LDHA double mutant Escherichia coli SS373 and the method of producing succinic acid therefrom.
Hespell Robert B. ; Wyckoff Herbert A. ; Dien Bruce S. ; Bothast Rodney J., Stabilization of pet operon plasmids and ethanol production in bacterial strains lacking lactate dehydrogenase and pyruvate formate lyase activities.
Somerville Christopher R. (Okemos MI) Poirier Yves (East Lansing MI) Dennis Douglas E. (Weyers Cave VA), Transgenic plants producing polyhydroxyalkanoates.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.