Engineered microorganisms for production of commodity chemicals and cellular biomass
申请人:The Regents of the University of California
公开号:US11332723B2
公开(公告)日:2022-05-17
The present disclosure provides methods of producing commodity products, the methods involving culturing a host cell that is genetically modified to produce a uronate dehydrogenase (UDH) that converts a sugar acid to its corresponding 1,5-aldonolactone, that uses NADP+ or NAD+ as a cofactor, and that produces NADPH or NADH, respectively, where the host cell coexpresses an endogenous or a heterologous reductase that utilizes the produced NADPH or NADH to generate the commodity product or a precursor thereof. The present disclosure provides a method of producing downstream products of glycerol and pyruvate in a genetically modified microbial host cell, the method involving culturing a genetically modified microbial host cell of the present disclosure in a culture medium comprising D-galacturonic acid. The present disclosure provides variant UDH polypeptides that utilize NADP+, nucleic acids encoding the variant UDH polypeptides; and host cells genetically modified with the nucleic acids.
本公开提供了生产商品产品的方法,该方法涉及培养宿主细胞,该宿主细胞经过基因改造,可产生一种尿酸脱氢酶(UDH),该酶可将一种糖酸转化为相应的1,5-醛内酯、该宿主细胞利用 NADP+ 或 NAD+ 作为辅助因子,并分别产生 NADPH 或 NADH,其中宿主细胞共同表达一种内源或异源还原酶,该还原酶利用所产生的 NADPH 或 NADH 生成商品或其前体。本公开提供了一种在转基因微生物宿主细胞中生产甘油和丙酮酸下游产物的方法,该方法涉及在包含D-半乳糖醛酸的培养基中培养本公开的转基因微生物宿主细胞。本公开提供了利用 NADP+ 的变体 UDH 多肽、编码变体 UDH 多肽的核酸以及用该核酸遗传修饰的宿主细胞。