美国南卡莱罗纳大学Li, Jie团队近日揭示了酰基亚砜酸天然产物亚砜霉素的发现及其生物合成特性。相关论文于2025年5月20日发表在《自然-化学》杂志上。

生命的有机分子由不同的官能团组成，这些官能团能够实现各种重要的生物功能。因此，在自然界中发现独特的官能团可以扩大人们对自然界的理解。研究组报告了亚砜霉素的基因组辅助发现，这是一种聚酮-非核糖体肽杂交天然产物，来自一种具有独特酰基亚砜酸功能的海洋链霉菌。 

通过一系列异源生物合成、功能遗传学和酶重构实验，研究组表明，这种先前描述的合成官能团是由一组来自初级和次级代谢的酶在生物学上组装而成的，包括一种黄素依赖性S-羟化酶，它使硫羧酸的硫原子羟基化。尽管到目前为止，公共数据库中还没有关于亚砜霉素生物合成基因簇的平行数据库，但催化酰基亚砜酸产生的酶在细菌基因组中广泛分布，这意味着这种不稳定的官能团可能同样在专门的代谢产物中广泛分布。

附：英文原文

Title: Discovery of acylsulfenic acid-featuring natural product sulfenicin and characterization of its biosynthesis

Author: Xue, Dan, Zou, Hongbin, Qiu, Yanping, Lv, Wei, Madden, Michael D., Xu, Mingming, Lian, Xiaoying, Pulliam, Conor, Older, Ethan A., Hou, Lukuan, Campbell, Andrew, de Rond, Tristan, Awakawa, Takayoshi, Yuan, Chunhua, Moore, Bradley S., Li, Jie

Issue&Volume: 2025-05-20

Abstract: Life’s organic molecules are built with diverse functional groups that enable various importance biological functions. As such, the discovery of unique functional groups in nature can expand our understanding of the natural world. Here we report the genome-aided discovery of sulfenicin, a polyketide–non-ribosomal peptide hybrid natural product from a marine Streptomyces bacterium bearing a unique acylsulfenic acid functionality. Through a series of heterologous biosynthesis, functional genetics and enzymatic reconstitution experiments, we show that this previously described synthetic functional group is biologically assembled by a set of enzymes from both primary and secondary metabolism, including a flavin-dependent S-hydroxylase that hydroxylates the sulfur atom of a thiocarboxylic acid. Although public databases so far include no parallel for the sulfenicin biosynthetic gene cluster, enzymes catalysing the production of acylsulfenic acid are widely distributed in bacterial genomes, implying that this labile functional group may similarly have a broad distribution among specialized metabolites.

DOI: 10.1038/s41557-025-01833-9

Source: https://www.nature.com/articles/s41557-025-01833-9