微生物来源天然产物中的β-甲基色氨酸单元及其生物合成研究进展

Biosynthesis of microbial natural products containing β-methyl tryptophan building blocks

微生物在次级代谢过程中通常会产生结构复杂、活性多样的天然产物。这些天然产物是新药发展的基础,亦可作为先导化合物或重要的药效基团用于药物研发。结构多样的氨基酸单元是参与合成复杂多样天然产物的重要前体。天然产物中的β-甲基氨基酸单元不仅可以赋予其生物活性,还能增强其生物稳定性而不被肽酶水解。本文综述了含有β-甲基氨基酸单元的天然产物,尤其对含有β-甲基色氨酸单元的天然产物生物合成途径进行了阐释。对β-甲基色氨酸单元生物合成途径的理解结合基因组数据有助于进行新结构天然产物的挖掘,并为运用代谢科学理念和合成生物学技术开发含有该单元的新化合物提供理论基础和可操作遗传元件。

Microorganisms are the resources for plentiful natural products with novel bioactivity and structural diversity,which can be used as leader compounds or pharmacophores for drug development.β-methyl amino acids have been found as promising components of abundant natural products.β-methyl amino acid-containing natural products often exhibit remarkable structure diversity together with enhanced biological stability,especially towards peptidases.In this review,we survey the knownβ-methyl amino acid-containing natural products,and summarize the biosynthetic mechanisms that formβ-methyl amino acids.Then,characterization of biosynthetic pathway ofβ-methyl tryptophan provides the platform to search new compound using genome mining,and creates novel architectures and bioactive compounds containingβ-methyl tryptophan moiety.