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    • 52. 发明授权
    • Organic acid-tolerant microorganisms and uses thereof for producing organic acids
    • 有机耐酸微生物及其用于生产有机酸的用途
    • US08715973B1
    • 2014-05-06
    • US13798835
    • 2013-03-13
    • Wisconsin Alumni Research Foundation
    • Brian Frederick PflegerMatthew Brett Begemann
    • C12P7/52C12P7/40C12P7/04C12N9/88C12P7/42
    • C12P7/52C12N1/12C12N9/93C12P7/40C12P7/42C12Y602/01001
    • Organic acid-tolerant microorganisms and methods of using same. The organic acid-tolerant microorganisms comprise modifications that reduce or ablate AcsA activity or AcsA homolog activity. The modifications increase tolerance of the microorganisms to such organic acids as 3-hydroxypropionic acid (3HP), acrylic acid, and propionic acid. Further modifications to the microorganisms such as increasing expression of malonyl-CoA reductase and/or acetyl-CoA carboxylase provide or increase the ability of the microorganisms to produce 3HP. Methods of generating an organic acid with the modified microorganisms are provided. Methods of using acsA or homologs thereof as counter-selectable markers include replacing acsA or homologs thereof in cells with genes of interest and selecting for the cells comprising the genes of interest with amounts of organic acids effective to inhibit growth of cells harboring acsA or the homologs.
    • 有机耐酸微生物及其使用方法。 有机耐酸微生物包括减少或消除AcsA活性或AcsA同系物活性的修饰。 这些修饰增加微生物对3-羟基丙酸(3HP),丙烯酸和丙酸等有机酸的耐受性。 对微生物的进一步修饰如增加丙二酰辅酶A还原酶和/或乙酰辅酶A羧化酶的表达提供或提高微生物产生3HP的能力。 提供了用改性微生物生成有机酸的方法。 使用acsA或其同系物作为反选择性标记的方法包括用感兴趣的基因替换细胞中的acsA或其同系物,并且选择含有有效基因的细胞的数量,所述有机酸有效抑制含有acsA或同源物的细胞生长 。