聚酮合酶
化学
聚酮
生物合成
酰基转移酶
乙酰辅酶A羧化酶
生物化学
代谢工程
蛋白质亚单位
立体化学
丙酮酸羧化酶
酶
基因
作者
Jun Zhang,Mengmeng Zheng,Jiayan Yan,Zixin Deng,Dongqing Zhu,Xudong Qu
标识
DOI:10.1021/acscatal.1c03818
摘要
The selective incorporation of new-to-nature extender units into polyketide synthesis is a highly effective way to engineer their carbon scaffolds. Currently, most atypical extender units are biosynthesized via reductive carboxylation of α,β-unsaturated thioesters catalyzed by crotonyl-CoA reductase/carboxylases or thioesterification of malonates by malonyl-CoA ligases followed by epimerase catalyzed enantiomerization. In this study, we identified an unusual β-subunit (Arm13) of the acyl-CoA carboxylase (ACCase) from the biosynthesis of armeniaspirols. This β-subunit is permissive to the α- and ε-subunits of propionyl-CoA carboxylase to form a fully active ACCase. Distinct from the other regular ACCases in substrate specificity, this ACCase can directly carboxylate medium chain acyl-CoAs ranging from C6 to C9 either with or without terminal substituents, e.g., alkyne or phenyl groups, to produce corresponding alkylmalonyl-CoAs with high catalytic efficiency. By harnessing the power of this ACCase in extender unit biosynthesis, we introduced structural variation into the carbon scaffold of armeniaspirols by feeding corresponding carboxylate precursors. These findings not only enrich the knowledge of the medium chain-specific ACCases but also provide an important biocatalyst for diversifying building blocks, which will greatly facilitate polyketide engineering.
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