Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Chembiochem. 2019 Apr 15;20(8):1039-1050. doi: 10.1002/cbic.201800640. Epub 2019 Mar 18.
Fogacin and two novel fogacin derivatives, fogacins B and C, were isolated from the rare actinomycete Actinoplanes missouriensis. Biosynthesis of fogacin C apparently requires β alkylation of a polyketide chain. The fogacin biosynthetic type II polyketide synthase (PKS) gene cluster contains a hydroxymethylglutaryl-coenzyme A synthase (HCS) cassette, which is usually responsible for β alkylation in the type I PKS system. Another characteristic of the fog cluster is that it encodes two sets of ketosynthase (KS) and chain-length factor (CLF). Inactivation of either of the two KS genes in A. missouriensis and heterologous expression of the HCS cassette with either of the two KS-CLF genes in Streptomyces albus indicated that each KS-CLF had a different starter substrate specificity: one preferred an unusual β-alkylated starter and the other preferred a normal acetyl starter. This study expands knowledge of HCS cassette-dependent β alkylation into the type II PKS system and provides a natural example of combinatorial biosynthesis for producing diverse polyketides from different starter substrates.
Fogacin 及其两种新型衍生物 fogacins B 和 C 从罕见放线菌 Actinoplanes missouriensis 中分离得到。Fogacin C 的生物合成显然需要聚酮链的β-烷基化。Fogacin 生物合成的 II 型聚酮合酶（PKS）基因簇包含羟甲基戊二酰辅酶 A 合酶（HCS）盒，该盒通常负责 I 型 PKS 系统中的β-烷基化。Fog 簇的另一个特征是它编码两套酮合酶（KS）和链长因子（CLF）。在 A. missouriensis 中敲除两个 KS 基因中的一个，以及在 Streptomyces albus 中用两个 KS-CLF 基因中的一个异源表达 HCS 盒，表明每个 KS-CLF 都具有不同的起始底物特异性：一个优先于不寻常的β-烷基化起始子，另一个优先于正常的乙酰化起始子。这项研究将 HCS 盒依赖性的β-烷基化扩展到 II 型 PKS 系统，并为利用不同起始底物组合生物合成产生不同聚酮化合物提供了一个天然范例。
