Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18361-6. doi: 10.1073/pnas.1210393109. Epub 2012 Oct 15.
Lanthionine-containing peptides (lanthipeptides) are a family of ribosomally synthesized and posttranslationally modified peptides containing (methyl)lanthionine residues. Here we present a phylogenomic study of the four currently known classes of lanthipeptide synthetases (LanB and LanC for class I, LanM for class II, LanKC for class III, and LanL for class IV). Although they possess very similar cyclase domains, class II-IV synthetases have evolved independently, and LanB and LanC enzymes appear to not always have coevolved. LanM enzymes from various phyla that have three cysteines ligated to a zinc ion (as opposed to the more common Cys-Cys-His ligand set) cluster together. Most importantly, the phylogenomic data suggest that for some scaffolds, the ring topology of the final lanthipeptides may be determined in part by the sequence of the precursor peptides and not just by the biosynthetic enzymes. This notion was supported by studies with two chimeric peptides, suggesting that the nisin and prochlorosin biosynthetic enzymes can produce the correct ring topologies of epilancin 15X and lacticin 481, respectively. These results highlight the potential of lanthipeptide synthetases for bioengineering and combinatorial biosynthesis. Our study also demonstrates unexplored areas of sequence space that may be fruitful for genome mining.
含硫醚的肽（硫肽）是一类核糖体合成和翻译后修饰的肽，含有（甲基）硫醚残基。在这里，我们对目前已知的四类硫肽合成酶（I 类的 LanB 和 LanC、II 类的 LanM、III 类的 LanKC 和 IV 类的 LanL）进行了系统发育基因组学研究。尽管它们具有非常相似的环化酶结构域，但 II 类-IV 类合成酶是独立进化的，LanB 和 LanC 酶似乎并不总是共同进化的。来自不同门的具有三个半胱氨酸与锌离子连接的 LanM 酶（与更常见的 Cys-Cys-His 配体集相反）聚集在一起。最重要的是，系统发育基因组学数据表明，对于某些支架，最终硫肽的环拓扑结构部分可能由前体肽的序列决定，而不仅仅由生物合成酶决定。这一观点得到了两个嵌合肽研究的支持，表明乳链菌肽和普罗氯素生物合成酶可以分别产生埃拉霉素 15X 和乳球菌素 481 的正确环拓扑结构。这些结果突出了硫肽合成酶在生物工程和组合生物合成中的潜力。我们的研究还表明了序列空间中未被探索的领域，这可能对基因组挖掘有很大的帮助。
