School of Chemistry and Biochemistry and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Nat Prod Rep. 2010 Feb;27(2):153-64. doi: 10.1039/b922434c. Epub 2009 Dec 7.
Thiopeptides, or thiazolylpeptides, are a family of highly modified peptide antibiotics first discovered several decades ago. Dozens of thiopeptides have since been identified, but, until recently, the biosynthetic genes responsible for their production remained elusive. The biosynthetic systems for a handful of thiopeptide metabolites were identified in the first portion of 2009. The surprising finding that these metabolites arise from the enzymatic tailoring of a simple, linear, ribosomally-synthesized precursor peptide led to a renewed appreciation of the architectural complexity accessible by posttranslational modification. This recent progress toward understanding thiopeptide antibiotic biosynthesis benefits the discovery of novel thiopeptides by either directed screening techniques or by mining available microbial genome sequences. Furthermore, access to the biosynthetic machinery now opens an avenue to the biosynthetic engineering of thiopeptide analogs. This Highlight discusses the genetic and biochemical insights revealed by these initial reports of the biosynthetic gene clusters for thiopeptide metabolites.
噻唑肽，或噻唑基肽，是一类高度修饰的肽类抗生素，最初于几十年前发现。此后已鉴定出数十种噻唑肽，但直到最近，其生物合成基因仍难以捉摸。2009 年的前半部分确定了少数几种噻唑肽代谢物的生物合成系统。令人惊讶的发现是，这些代谢物是由简单的、线性的、核糖体合成的前体肽的酶促修饰产生的，这使得人们重新认识到了通过翻译后修饰可获得的结构复杂性。由于这一最新进展，人们对噻唑肽抗生素生物合成的理解有助于通过定向筛选技术或挖掘可用微生物基因组序列来发现新型噻唑肽。此外，获得生物合成机制为噻唑肽类似物的生物合成工程开辟了新途径。本文重点讨论了这些噻唑肽代谢物生物合成基因簇的初步报告所揭示的遗传和生化见解。
