Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis.
Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis.
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DOI：
10.1039/c6sc02803a
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发表时间：
2017-01-01
期刊：
影响因子：
8.4
通讯作者：
Challis GL
中科院分区：
文献类型：
--
作者：
Awodi UR;Ronan JL;Masschelein J;de Los Santos ELC;Challis GL
聚酮合酶还原链释放和随后的转氨作用是放线菌中聚酮生物碱生物合成的关键步骤。放线菌产生多种具有不寻常结构的聚酮生物碱。最近，研究表明，I 型模块化聚酮合酶 (PKS) 参与了 Coelimycin P1 的组装，coelimycin P1 是一种由天蓝色链霉菌 M145 产生的聚酮生物碱。然而，将 PKS 产物转化为 coelimycin P1 的机制仍有待阐明。在这里，我们表明 PKS 的 C 端硫酯还原酶 (TR) 结构域和 ω-转氨酶负责将聚酮化合物链释放为醛及其随后的还原胺化。生物信息学分析确定了放线菌基因组中的许多基因簇，这些基因簇编码具有 C 端 TR 结构域和 ω-转氨酶同源物的模块化 PKS。预计它们将指导已知和新型聚酮生物碱的生物合成，表明还原链释放和转氨作用构成此类代谢物生物合成的保守机制。
Polyketide synthase reductive chain release and subsequent transamination are key steps in the biosynthesis of polyketide alkaloids in actinobacteria. Actinobacteria produce a variety of polyketide alkaloids with unusual structures. Recently, it was shown that a type I modular polyketide synthase (PKS) is involved in the assembly of coelimycin P1, a polyketide alkaloid produced by Streptomyces coelicolor M145. However, the mechanisms for converting the product of the PKS to coelimycin P1 remain to be elucidated. Here we show that the C-terminal thioester reductase (TR) domain of the PKS and an ω-transaminase are responsible for release of the polyketide chain as an aldehyde and its subsequent reductive amination. Bioinformatics analyses identified numerous gene clusters in actinobacterial genomes that encode modular PKSs with a C-terminal TR domain and a homolog of the ω-transaminase. These are predicted to direct the biosynthesis of both known and novel polyketide alkaloids, suggesting that reductive chain release and transamination constitutes a conserved mechanism for the biosynthesis of such metabolites.