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1. 发明授权

US11697830B2 Iterative platform for the synthesis of alpha functionalized products 有权
公开(公告)号：US11697830B2
公开(公告)日：2023-07-11
申请号：US16818642
申请日：2020-03-13
申请人： Ramon Gonzalez , James M. Clomburg , Seokjung Cheong
发明人： Ramon Gonzalez , James M. Clomburg , Seokjung Cheong
IPC分类号： C12N9/02 , C12P7/42 , C12N9/00 , C12N9/10 , C12N9/04 , C12N9/16 , C12N9/88
CPC分类号： C12P7/42 , C12N9/001 , C12N9/0006 , C12N9/0008 , C12N9/1029 , C12N9/13 , C12N9/16 , C12N9/88 , C12N9/93 , C12Y101/01036 , C12Y102/0101 , C12Y103/01044 , C12Y402/01119
摘要： The use of microorganisms to make alpha-functionalized chemicals and fuels, (e.g. alpha-functionalized carboxylic acids, alcohols, hydrocarbons, amines, and their beta-, and omega-functionalized derivatives), by utilizing an iterative carbon chain elongation pathway that uses functionalized extender units. The core enzymes in the pathway include thiolase, dehydrogenase, dehydratase and reductase. Native or engineered thiolases catalyze the condensation of either unsubstituted or functionalized acyl-CoA primers with an alpha-functionalized acetyl-CoA as the extender unit to generate alpha-functionalized β-keto acyl-CoA. Dehydrogenase converts alpha-functionalized β-keto acyl-CoA to alpha-functionalized β-hydroxy acyl-CoA. Dehydratase converts alpha-functionalized β-hydroxy acyl-CoA to alpha-functionalized enoyl-CoA. Reductase converts alpha-functionalized enoyl-CoA to alpha-functionalized acyl-CoA. The platform can be operated in an iterative manner (i.e. multiple turns) by using the resulting alpha-functionalized acyl-CoA as primer and the aforementioned alpha-functionalized extender unit in subsequent turns of the cycle. Termination pathways acting on any of the four alpha-functionalized CoA thioester intermediates terminate the platform and generate various alpha-functionalized carboxylic acids, alcohols and amines with different β-reduction degree.

2. 发明授权

US11781120B2 Biosynthesis of polyketides 有权
公开(公告)号：US11781120B2
公开(公告)日：2023-10-10
申请号：US16930220
申请日：2020-07-15
申请人： Ramon Gonzalez
发明人： Ramon Gonzalez , Seokjung Cheong , James M. Clomburg
IPC分类号： C12N9/10 , C12P15/00 , C12P17/06
CPC分类号： C12N9/1025 , C12P17/06 , C12Y203/01174
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.

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