Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Republic of Korea.
Appl Microbiol Biotechnol. 2010 Feb;85(5):1227-39. doi: 10.1007/s00253-009-2326-8. Epub 2009 Nov 10.
Polyketides comprise one of the major families of natural products. They are found in a wide variety of bacteria, fungi, and plants and include a large number of medically important compounds. Polyketides are biosynthesized by polyketide synthases (PKSs). One of the major groups of polyketides are the macrolides, the activities of which are derived from the presence of a macrolactone ring to which one or more 6-deoxysugars are attached. The core macrocyclic ring is biosynthesized from acyl-CoA precursors by PKS. Genetic manipulation of PKS-encoding genes can result in predictable changes in the structure of the macrolactone component, many of which are not easily achieved through standard chemical derivatization or total synthesis. Furthermore, many of the changes, including post-PKS modifications such as glycosylation and oxidation, can be combined for further structural diversification. This review highlights the current state of novel macrolide production with a focus on the genetic engineering of PKS and post-PKS tailoring genes. Such engineering of the metabolic pathways for macrolide biosynthesis provides attractive alternatives for the production of diverse non-natural compounds. Other issues of importance, including the engineering of precursor pathways and heterologous expression of macrolide biosynthetic genes, are also considered.
聚酮类化合物是天然产物的主要家族之一。它们存在于各种细菌、真菌和植物中，包括许多具有重要医学意义的化合物。聚酮类化合物是由聚酮合酶（PKS）生物合成的。聚酮类化合物的主要类群之一是大环内酯类，其活性来源于大环内酯环的存在，其上连接有一个或多个 6-去氧糖。核心大环通过 PKS 由酰基辅酶 A 前体生物合成。对编码 PKS 的基因进行遗传操作可以导致大环内酯成分的结构发生可预测的变化，其中许多变化通过标准的化学衍生化或全合成是不容易实现的。此外，许多变化，包括聚酮后修饰如糖基化和氧化，可以组合进行进一步的结构多样化。本文综述了新型大环内酯类化合物生产的最新进展，重点介绍了 PKS 和聚酮后修饰基因的遗传工程。这种对大环内酯类生物合成代谢途径的工程设计为生产各种非天然化合物提供了有吸引力的替代方法。其他重要问题，包括前体途径的工程设计和大环内酯生物合成基因的异源表达，也得到了考虑。
