期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：46
页码：12940-12945
DOI：10.1073/pnas.1613285113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceBacteria use small molecules to mediate their relationships with nearby microbes, and these molecules represent both a promising source of therapeutic agents and a model system for the evolution and dissemination of molecular diversity. This study deals with one such molecule, selvamicin, which is produced by ant-associated bacteria. These bacteria protect the ants nests against fungal pathogens. Selvamicin is an atypical member of a clinically important class of antifungal agents, and it appears to have both better therapeutic properties and a different mechanism of action. Further, the genes for producing it are found on the bacterias chromosome in one ant nest but on a plasmid in another, illustrating the likely path by which it has spread. The bacteria harbored by fungus-growing ants produce a variety of small molecules that help maintain a complex multilateral symbiosis. In a survey of antifungal compounds from these bacteria, we discovered selvamicin, an unusual antifungal polyene macrolide, in bacterial isolates from two neighboring ant nests. Selvamicin resembles the clinically important antifungals nystatin A1 and amphotericin B, but it has several distinctive structural features: a noncationic 6-deoxymannose sugar at the canonical glycosylation site and a second sugar, an unusual 4-O-methyldigitoxose, at the opposite end of selvamicins shortened polyene macrolide. It also lacks some of the pharmacokinetic liabilities of the clinical agents and appears to have a different target. Whole genome sequencing revealed the putative type I polyketide gene cluster responsible for selvamicins biosynthesis including a subcluster of genes consistent with selvamicins 4-O-methyldigitoxose sugar. Although the selvamicin biosynthetic cluster is virtually identical in both bacterial producers, in one it is on the chromosome, in the other it is on a plasmid. These alternative genomic contexts illustrate the biosynthetic gene cluster mobility that underlies the diversity and distribution of chemical defenses by the specialized bacteria in this multilateral symbiosis.
