The hidden enzymology of bacterial natural product biosynthesis

被引:67
|
作者
Scott, Thomas A. [1 ]
Piel, Jorn [1 ]
机构
[1] Swiss Fed Inst Technol, Inst Microbiol, Zurich, Switzerland
基金
瑞士国家科学基金会; 欧洲研究理事会;
关键词
THIOETHER BOND FORMATION; SIDE-RING-SYSTEM; POLYCYCLIC TETRAMATE MACROLACTAMS; S-ADENOSYLMETHIONINE PROTEIN; RADICAL SAM ENZYMES; NONRIBOSOMAL PEPTIDE; GENE-CLUSTER; HETEROLOGOUS EXPRESSION; POLYKETIDE SYNTHASE; MASS-SPECTROMETRY;
D O I
10.1038/s41570-019-0107-1
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Bacterial natural products display astounding structural diversity, which, in turn, endows them with a remarkable range of biological activities that are of significant value to modern society. Such structural features are generated by biosynthetic enzymes that construct core scaffolds or perform peripheral modifications, and can thus define natural product families, introduce pharmacophores and permit metabolic diversification. Modern genomics approaches have greatly enhanced our ability to access and characterize natural product pathways via sequence-similarity-based bioinformatics discovery strategies. However, many biosynthetic enzymes catalyse exceptional, unprecedented transformations that continue to defy functional prediction and remain hidden from us in bacterial (nneta)genonnic sequence data. In this Review, we highlight exciting examples of unusual enzymology that have been uncovered recently in the context of natural product biosynthesis. These suggest that much of the natural product diversity, including entire substance classes, awaits discovery. New approaches to lift the veil on the cryptic chemistries of the natural product universe are also discussed.
引用
收藏
页码:404 / 425
页数:22
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