Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama Meguro-ku, Tokyo, 152-8551, Japan.
Chembiochem. 2022 Jul 19;23(14):e202200200. doi: 10.1002/cbic.202200200. Epub 2022 May 16.
The ketosynthase (KS) domain is a core domain found in modular polyketide synthases (PKSs). To maintain the polyketide biosynthetic fidelity, the KS domain must only accept an acyl group from the acyl carrier protein (ACP) domain of the immediate upstream module even when they are separated into different polypeptides. Although it was reported that both the docking domain-based interactions and KS-ACP compatibility are important for the interpolypeptide transacylation reaction in 6-deoxyerythronolide B synthase, it is not clear whether these findings are broadly applied to other modular PKSs. Herein, we describe the importance of protein-protein recognition in the intermodular transacylation between VinP1 module 3 and VinP2 module 4 in vicenistatin biosynthesis. We compared the transacylation activity and crosslinking efficiency of VinP2 KS against the cognate VinP1 ACP with the noncognate one. As a result, it appeared that VinP2 KS distinguishes the cognate ACP from other ACPs.
酮合酶 (KS) 结构域是模块化聚酮合酶 (PKS) 中的核心结构域。为了保持聚酮生物合成的保真度，KS 结构域只能接受来自紧邻上游模块的酰基载体蛋白 (ACP) 结构域的酰基基团，即使它们被分成不同的多肽。尽管据报道，在 6-脱氧赤藓醇 B 合酶中，基于对接结构域的相互作用和 KS-ACP 兼容性对于多肽间转酰基反应很重要，但尚不清楚这些发现是否广泛适用于其他模块化 PKS。本文描述了在威斯塔汀生物合成中 VinP1 模块 3 和 VinP2 模块 4 之间的模块间转酰基反应中蛋白质-蛋白质识别的重要性。我们比较了 VinP2 KS 对同源 VinP1 ACP 的转酰基活性和交联效率与非同源 ACP 的。结果表明，VinP2 KS 能够区分同源 ACP 和其他 ACP。
