| Literature DB >> 26877024 |
Manuel A Ortega1, Yue Hao1, Mark C Walker2, Stefano Donadio3, Margherita Sosio3, Satish K Nair1,4, Wilfred A van der Donk1,2.
Abstract
Class I lantibiotic dehydratases dehydrate selected Ser/Thr residues of a precursor peptide. Recent studies demonstrated the requirement of glutamyl-tRNA(Glu) for Ser/Thr activation by one of these enzymes (NisB) from the Firmicute Lactococcus lactis. However, the generality of glutamyl-tRNA(Glu) usage and the tRNA specificity of lantibiotic dehydratases have not been established. Here we report the 2.7-Å resolution crystal structure, along with the glutamyl-tRNA(Glu) utilization of MibB, a lantibiotic dehydratase from the Actinobacterium Microbispora sp. 107891 involved in the biosynthesis of the clinical candidate NAI-107. Biochemical assays revealed nucleotides A73 and U72 within the tRNA(Glu) acceptor stem to be important for MibB glutamyl-tRNA(Glu) usage. Using this knowledge, an expression system for the production of NAI-107 analogs in Escherichia coli was developed, overcoming the inability of MibB to utilize E. coli tRNA(Glu). Our work provides evidence for a common tRNA(Glu)-dependent dehydration mechanism, paving the way for the characterization of lantibiotics from various phyla.Entities:
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Year: 2016 PMID: 26877024 PMCID: PMC4798866 DOI: 10.1016/j.chembiol.2015.11.017
Source DB: PubMed Journal: Cell Chem Biol ISSN: 2451-9448 Impact factor: 8.116