组合生物合成聚酮类药物研究进展

Advance in polyketide drugs from combinatorial biosynthesis

在筛选和发展新型微生物药物方面组合生物合成日益成为生物、化学和医药界关注的重点。基于聚酮类(PK)天然产物的独特化学结构和良好生物活性,研究它们的生物合成机制,将为合理化遗传修饰生物合成途径获得结构类似物提供遗传和生物化学的基础,实现利用现代生物学和化学的技术手段在微生物体内进行药物开发的目的。现综述近年来组合生物合成技术的基本原理、聚酮合酶的基本作用机制以及合成途径的改造情况等。

Combinatorial biosynthesis is becoming the focus of intense research activity of drug discovery and development in the fields of biology, chemistry and medical sciences. Based on the unusual molecular architecture and phenomenal biological activities of natural products, particularly polyketides, elucidation of their biosynthetic machineries is laying the genetic and biochemical foundation of novel analogues that are generated by rational biosynthetic pathways, and eventually facilitates the application of biological and chemical technology to meet the challenge of drug discovery and development in microorganisms. This article briefly introduced the status of combinatorial biosynthesis technology in microbial medicine researches including polyketides and the machineries of three types of polyketide synthase.