2MW3

Solution NMR structure of the lasso peptide streptomonomicin

Summary for 2MW3

• Entry DOI: 10.2210/pdb2mw3/pdb
• NMR Information: BMRB: 25297
• Descriptor: Lasso peptide (1 entity in total)
• Functional Keywords: lasso peptide, antibiotic, macrocycle, ripp, unknown function
• Biological source: Streptomonospora alba
• Total number of polymer chains: 1
• Total formula weight: 2252.56

Authors

Tietz, J.I.,Zhu, L.,Mitchell, D.A.,Metelev, M.,Melby, J.O.,Blair, P.M.,Livnat, I.,Severinov, K. (deposition date: 2014-10-24, release date: 2015-01-28, Last modification date: 2024-10-16)

Primary citation

Metelev, M.,Tietz, J.I.,Melby, J.O.,Blair, P.M.,Zhu, L.,Livnat, I.,Severinov, K.,Mitchell, D.A.
Structure, bioactivity, and resistance mechanism of streptomonomicin, an unusual lasso Peptide from an understudied halophilic actinomycete.
Chem.Biol., 22:241-250, 2015

PubMed 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.

PubMed: 25601074
DOI: 10.1016/j.chembiol.2014.11.017

Experimental method

SOLUTION NMR