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    • 42. 发明申请
    • METHODS AND ORGANISMS FOR GROWTH-COUPLED PRODUCTION OF 3-HYDROXYPROPIONIC ACID
    • 生长3-羟基丙酸生产的方法和机理
    • WO2008091627A2
    • 2008-07-31
    • PCT/US2008/000861
    • 2008-01-22
    • GENOMATICA, INC.BURGARD, Anthony, P.VAN DIEN, Stephen, J.
    • BURGARD, Anthony, P.VAN DIEN, Stephen, J.
    • C12N1/00
    • C12N15/52C12N9/00C12P7/42
    • The invention provides a non-naturally occurring microorganism having one or more gene disruptions, the one or more gene disruptions occurring in genes encoding an enzyme obligatory coupling 3-hydroxypropionic acid production to growth of the microorganism when the gene disruption reduces an activity of the enzyme, whereby the one or more gene disruptions confers stable growth-coupled production of 3-hydroxypropionic acid onto the non-naturally occurring microorganism. Also provided is a non-naturally occurring microorganism comprising a set of metabolic modifications obligatory coupling 3-hydroxypropionic acid production to growth of the microorganism, the set of metabolic modifications having disruption of one or more genes including: (a) the set of genes selected from: (1) adhE, ldhA, pta-ackA; (2) adhE, ldhA, frdABCD; (3) adhE, ldhA, frdABCD, ptsG; (4) adhE, ldhA, frdABCD, pntAB; (5) adhE, ldhA, fumA, fumB, fumC; (6) adhE, ldhA, fumA, fumB, fumC, pntAB; (7) pflAB, ldhA, or (8) adhE, ldhA, pgi in a microorganism utilizing an anaerobic β-alanine 3-HP precursor pathway; (b) the set of genes selected from: (1) tpi, zwf; (2) tpi, ybhE; (3) tpi, gnd; (4) fpb, gapA; (5) pgi, edd, or (6) pgi, eda in a microorganism utilizing an aerobic glycerol 3-HP precursor pathway; (c) the set of genes selected from: (1) eno ; (2) yibO ; (3) eno , atpH, or other atp subunit, or (4) yibO , atpH , or other atp subunit, in a microorganism utilizing a glycerate 3-HP precursor pathway, or an ortholog thereof, wherein the microorganism exhibits stable growth- coupled production of 3-hydroxypropionic acid. The disruptions can be complete gene disruptions and the non-naturally occurring organisms can include a variety of prokaryotic or eukaryotic microorganisms. A method of producing a non-naturally occurring microorganism having stable growth-coupled production of 3-hydroxypropionic acid is further provided. The method includes: (a) identifying in silico a set of metabolic modifications requiring 3-hydroxypropionic acid production during exponential growth, and (b) genetically modifying a microorganism to contain the set of metabolic modifications requiring 3-hydroxypropionic acid production.
    • 本发明提供了一种具有一个或多个基因破坏的非天然存在的微生物,当基因破坏降低酶的活性时,编码酶强制性偶合3-羟基丙酸产生的微生物生长的基因中发生的一种或多种基因破坏 由此一个或多个基因破坏赋予非天然存在的微生物上3-羟基丙酸的稳定生长偶联产生。 还提供了非天然存在的微生物,其包含一系列代谢修饰,其强制性将3-羟基丙酸生产偶联至微生物生长,该组代谢修饰具有破坏一个或多个基因,包括:(a)所选择的一组基因 来自:(1)adhE,ldhA,pta-ackA; (2)adhE,ldhA,frdABCD; (3)adhE,ldhA,frdABCD,ptsG; (4)adhE,ldhA,frdABCD,pntAB; (5)adhE,ldhA,fumA,fumB,fumC; (6)adhE,ldhA,fumA,fumB,fumC,pntAB; (7)pflAB,ldhA或(8)adhE,ldhA,pgi在使用厌氧β-丙氨酸3-HP前体途径的微生物中; (b)选自以下的一组基因:(1)tpi,zwf; (2)tpi,ybhE; (3)tpi,gnd; (4)fpb,gapA; (5)pgi,edd或(6)pgi,eda在利用有氧甘油3-HP前体途径的微生物中; (c)选自以下的一组基因:(1)eno; (2)yibo; (3)eno,atpH或其他atp亚基,或(4)yibO,atpH或其他atp亚基,使用甘油3-HP前体途径的微生物或其直系同源物,其中所述微生物表现出稳定的生长耦合 生产3-羟基丙酸。 破坏可能是完全的基因破坏,非天然存在的生物体可以包括多种原核或真核微生物。 还提供了一种生产具有稳定的3-羟基丙酸的生长偶联生产的非天然存在的微生物的方法。 该方法包括:(a)在指数生长过程中,以计算机识别需要3-羟基丙酸生成的一组代谢修饰,和(b)遗传修饰微生物以包含需要3-羟基丙酸生产的一组代谢修饰。
    • 43. 发明申请
    • MICROORGANISMS AND METHODS FOR IMPROVING PRODUCT YIELDS ON METHANOL USING ACETYL-COA SYNTHESIS
    • 使用乙酰辅酶A合成改善甲醇产品的微生物和方法
    • WO2015084633A1
    • 2015-06-11
    • PCT/US2014/067287
    • 2014-11-25
    • GENOMATICA, INC.
    • OSTERHOUT, Robin, E.BURGARD, Anthony, P.PHARKYA, PritiANDRAE, Stefan
    • C12N1/19C12N1/15C12N1/13C12N1/11
    • C12P5/026C12N1/14C12N1/20C12N15/70C12N15/81C12P7/02C12P7/04C12P7/18C12P7/40C12P7/42C12P7/44C12P13/001C12P13/005C12P17/10Y02E50/343
    • The invention provides non-naturally occurring microbial organisms containing enzymatic pathways and/or metabolic modifications for enhancing carbon flux through acetyl-CoA. In some embodiments, the microbial organisms having such pathways also include pathways for generating reducing equivalents, formaldehyde fixation and/or formate assimilation. The enhanced carbon flux through acetyl-CoA, in combination with pathways for generating reducing equivalents, formaldehyde fixation and/or formate assimilation can, in some embodiments, be used for production of a bioderived compound. Accordingly, in some embodiments, the microbial organisms of the invention can include a pathway capable of producing a bioderived compound of the invention. The invention still further provides a bioderived compound produced by a microbial organism of the invention, culture medium having the bioderived compound of the invention, compositions having the bioderived compound of the invention, a biobased product comprising the bioderived compound of the invention, and a process for producing a bioderived compound of the invention.
    • 本发明提供了非天然存在的微生物,其含有通过乙酰辅酶A的碳通量的酶途径和/或代谢修饰。 在一些实施方案中,具有这种途径的微生物生物体还包括产生还原当量的途径,甲醛固定和/或甲酸盐同化。 在一些实施方案中,通过乙酰辅酶A增强的碳通量与产生还原当量的途径,甲醛固定和/或甲酸盐同化可用于生产生物活性化合物。 因此,在一些实施方案中,本发明的微生物体可以包括能够产生本发明生物活性化合物的途径。 本发明还提供了由本发明的微生物生物产生的生物活性化合物,具有本发明的生物活性化合物的培养基,具有本发明的生物活性化合物的组合物,包含本发明的生物活性化合物的生物基产物和一种方法 用于生产本发明的生物活性化合物。