Selvamicin, an atypical antifungal polyene from two alternative genomic contexts.

Citation data:

Proceedings of the National Academy of Sciences of the United States of America, ISSN: 1091-6490, Vol: 113, Issue: 46, Page: 12940-12945

Publication Year:
2016
Usage 132
Abstract Views 100
Downloads 29
Link-outs 3
Captures 71
Readers 67
Exports-Saves 4
Social Media 20
Tweets 12
Shares, Likes & Comments 8
Citations 23
Citation Indexes 23
Repository URL:
http://www.pnas.org/content/113/46/12940#aff-1; http://hdl.handle.net/10669/30392
PMID:
27803316
DOI:
10.1073/pnas.1613285113
PMCID:
PMC5135293
Author(s):
Van Arnam, Ethan B.; Ruzzini, Antonio C.; Sit, Clarissa S.; Horn, Heidi A.; Pinto Tomás, Adrián A.; Currie, Cameron R.; Clardy, Jon
Publisher(s):
Proceedings of the National Academy of Sciences
Tags:
Multidisciplinary; Antifungal; Horizontal gene transfer; Biosynthesis; Symbiosis; Natural products
Most Recent Tweet View All Tweets
article description
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 A 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 selvamicin's 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 selvamicin's biosynthesis including a subcluster of genes consistent with selvamicin's 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.