Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Beutenbergstr. 11a, 07745 Jena, Germany; Chair of Natural Product Chemistry, Friedrich Schiller University, Jena, Germany.
Trends Biochem Sci. 2015 Apr;40(4):189-99. doi: 10.1016/j.tibs.2015.02.001. Epub 2015 Mar 7.
Bacterial modular type I polyketide synthases (PKSs) represent giant megasynthases that produce a vast number of complex polyketides, many of which are pharmaceutically relevant. This review highlights recent advances in elucidating the mechanism of bacterial type I PKSs and associated enzymes, and outlines the ramifications of this knowledge for synthetic biology approaches to expand structural diversity. New insights into biosynthetic codes and structures of thiotemplate systems pave the way to rational bioengineering strategies. Through advances in genome mining, DNA recombination technologies, and biochemical analyses, the toolbox of non-canonical polyketide-modifying enzymes has been greatly enlarged. In addition to various chain-branching and chain-fusing enzymes, an increasing set of scaffold modifying biocatalysts is now available for synthetically hard-to-emulate reactions.
细菌模块化 I 型聚酮合酶 (PKSs) 代表了产生大量复杂聚酮化合物的巨型 megasynthases，其中许多与药物相关。本综述重点介绍了阐明细菌 I 型 PKS 及其相关酶的机制的最新进展，并概述了这些知识对扩大结构多样性的合成生物学方法的影响。对硫模板系统生物合成代码和结构的新见解为合理的生物工程策略铺平了道路。通过基因组挖掘、DNA 重组技术和生化分析的进展，非典型聚酮修饰酶的工具包得到了极大的扩展。除了各种链分支和链融合酶外，现在还可以获得越来越多的支架修饰生物催化剂，用于模拟困难的合成反应。
