发明名称 |
BIOSYNTHESIS OF POLYKETIDES |
摘要 |
This disclosure generally relates to the use of microorganisms to make various functionalized polyketides through polyketoacyl-CoA thiolase-catalyzed non-decarboxylative condensation reactions instead of decarboxylative reactions catalyzed by polyketide synthases. Native or engineered polyketoacyl-CoA thiolases catalyze the non-decarboxylative Claisen condensation in an iterative manner (i.e. multiple rounds) between two either unsubstituted or functionalized ketoacyl-CoAs (and polyketoacyl-CoAs) serving as the primers and acyl- CoAs serving as the extender unit to generate (and elongate) polyketoacyl-CoAs. Before the next round of polyketoacyl-CoA thiolase reaction, the β-keto group of the polyketide chain of polyketoacyl-CoA can be reduced and modified step-wise by 3-OH-polyketoacyl-CoA dehydrogenase or polyketoenoyl-CoA hydratase or polyketoenoyl-CoA reductase. Dehydrogenase converts the β-keto group to β-hydroxy group. Hydratase converts the β- hydroxy group to α-β-double-bond. Reductase converts the α-β-double-bond to single bond. Spontaneous or thioesterase catalyzed termination reaction terminates the elongation of polyketide chain of polyketoacyl-CoA at any point through CoA removal and spontaneous reactions rearrange the structure, generating the final functional polyketide products. |
申请公布号 |
WO2017020043(A2) |
申请公布日期 |
2017.02.02 |
申请号 |
WO2016US45037 |
申请日期 |
2016.08.01 |
申请人 |
WILLIAM MARSH RICE UNIVERSITY |
发明人 |
GONZALEZ, Ramon;CHEONG, Seokjung;CLOMBURG, James, M. |
分类号 |
C12P7/40;C12N1/21 |
主分类号 |
C12P7/40 |
代理机构 |
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代理人 |
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