来自苦霉素聚酮合酶的单模块的底物识别与通道化

Substrate recognition and channeling of monomodules from the pikromycin polyketide synthase.

作者信息

Beck Brian J, Aldrich Courtney C, Fecik Robert A, Reynolds Kevin A, Sherman David H

机构信息

Department of Microbiology and Biotechnology Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.

出版信息

J Am Chem Soc. 2003 Oct 15;125(41):12551-7. doi: 10.1021/ja034841s.

DOI:10.1021/ja034841s

PMID:14531700

Abstract

The unique ability of the pikromycin (Pik) polyketide synthase to generate 12- and 14-membered ring macrolactones presents an opportunity to explore the fundamental processes underlying polyketide synthesis, specifically the mechanistic details of the chain extension process. We have overexpressed and purified PikAIII (module 5) and PikAIV (module 6) and assessed the ability of these proteins to generate tri- and tetraketide lactone products using N-acetylcysteamine-activated diketides and (14)C-methylmalonyl-CoA as substrates. Comparison of the stereochemical specificities for PikAIII and PikAIV and the reported values for the DEBS modules reveals significant differences between these systems.

摘要

苦霉素（Pik）聚酮合酶生成12元和14元大环内酯的独特能力为探索聚酮合成的基本过程提供了契机，特别是链延伸过程的机制细节。我们已经对PikAIII（模块5）和PikAIV（模块6）进行了过表达和纯化，并使用N-乙酰半胱胺活化的二酮化合物和（14）C-甲基丙二酰辅酶A作为底物，评估了这些蛋白质生成三酮和四酮内酯产物的能力。PikAIII和PikAIV的立体化学特异性与已报道的DEBS模块的值的比较揭示了这些系统之间的显著差异。