Biosynthesis of Diverse Antimicrobial and Antiproliferative Acyloins in Anaerobic Bacteria

Metabolic profiling and genome mining revealed that anaerobic bacteria have the potential to produce acyloin natural products. In addition to sattazolin A and B, three new sattazolin congeners and a novel acyloin named clostrocyloin were isolated from three strains of Clostridium beijerinckii, a bac...

Full description

Saved in:
Bibliographic Details
Published in:ACS chemical biology 2019-07, Vol.14 (7), p.1490-1497
Main Authors: Schieferdecker, Sebastian, Shabuer, Gulimila, Letzel, Anne-Catrin, Urbansky, Barbara, Ishida-Ito, Mie, Ishida, Keishi, Cyrulies, Michael, Dahse, Hans-Martin, Pidot, Sacha, Hertweck, Christian
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antifungal Agents - chemistry
Antifungal Agents - pharmacology
Bacteria, Anaerobic - chemistry
Biosynthetic Pathways
Clostridium - chemistry
Fatty Alcohols - chemistry
Fatty Alcohols - pharmacology
Hexanones - chemistry
Hexanones - pharmacology
Humans
Indoles - chemistry
Indoles - pharmacology
Mycobacterium - drug effects
Mycobacterium Infections - drug therapy
Mycoses - drug therapy
Pseudomonas - drug effects
Pseudomonas Infections - drug therapy
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Metabolic profiling and genome mining revealed that anaerobic bacteria have the potential to produce acyloin natural products. In addition to sattazolin A and B, three new sattazolin congeners and a novel acyloin named clostrocyloin were isolated from three strains of Clostridium beijerinckii, a bacterium used for industrial solvent production. Bioactivity profiling showed that the sattazolin derivatives possess antimicrobial activities against mycobacteria and pseudomonads with only low cytotoxicity. Clostrocyloin was found to be mainly active against fungi. The thiamine diphosphate (ThDP)-dependent sattazolin-producing synthase was identified in silico and characterized both in vivo and in in vitro enzyme assays. A related acyloin synthase from the clostrocyloin producer was shown to be responsible for the production of the acyloin core of clostrocyloin. The biotransformation experiments provided first insights into the substrate scope of the clostrocyloin synthase and revealed biosynthetic intermediates.
ISSN:1554-8929
1554-8937
DOI:10.1021/acschembio.9b00228