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Chem Biol. 2015 Feb 19;22(2):241-50. doi: 10.1016/j.chembiol.2014.11.017. Epub 2015 Jan 15.

Structure, bioactivity, and resistance mechanism of streptomonomicin, an unusual lasso Peptide from an understudied halophilic actinomycete.

Author information

1
Institute for Nanobiotechnologies, Saint Petersburg State Polytechnical University, Saint Petersburg 195251, Russia; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
2
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
3
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
4
NMR Laboratory, School of Chemical Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
5
Institute for Nanobiotechnologies, Saint Petersburg State Polytechnical University, Saint Petersburg 195251, Russia; Department of Molecular Biology and Biochemistry, Waksman Institute for Microbiology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
6
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: douglasm@illinois.edu.

Abstract

Natural products are the most historically significant source of compounds for drug development. However, unacceptably high rates of compound rediscovery associated with large-scale screening of common microbial producers have resulted in the abandonment of many natural product drug discovery efforts, despite the increasing prevalence of clinically problematic antibiotic resistance. Screening of underexplored taxa represents one strategy to avoid rediscovery. Herein we report the discovery, isolation, and structural elucidation of streptomonomicin (STM), an antibiotic lasso peptide from Streptomonospora alba, and report the genome for its producing organism. STM-resistant clones of Bacillus anthracis harbor mutations to walR, the gene encoding a response regulator for the only known widely distributed and essential two-component signal transduction system in Firmicutes. To the best of our knowledge, Streptomonospora had been hitherto biosynthetically and genetically uncharacterized, with STM being the first reported compound from the genus. Our results demonstrate that understudied microbes remain fruitful reservoirs for the rapid discovery of novel, bioactive natural products.

PMID:
25601074
PMCID:
PMC4336579
DOI:
10.1016/j.chembiol.2014.11.017
[Indexed for MEDLINE]
Free PMC Article

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