Structural highlights
Publication Abstract from PubMed
Class I lantibiotic dehydratases dehydrate selected Ser/Thr residues of a precursor peptide. Recent studies demonstrated the requirement of glutamyl-tRNAGlu for Ser/Thr activation by one of these enzymes (NisB) from the Firmicute Lactococcus lactis. However, the generality of glutamyl-tRNAGlu usage and the tRNA specificity of lantibiotic dehydratases have not been established. Here we report the 2.7-A resolution crystal structure, along with the glutamyl-tRNAGlu 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 tRNAGlu acceptor stem to be important for MibB glutamyl-tRNAGlu 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 tRNAGlu. Our work provides evidence for a common tRNAGlu-dependent dehydration mechanism, paving the way for the characterization of lantibiotics from various phyla.
Structure and tRNA Specificity of MibB, a Lantibiotic Dehydratase from Actinobacteria Involved in NAI-107 Biosynthesis.,Ortega MA, Hao Y, Walker MC, Donadio S, Sosio M, Nair SK, van der Donk WA Cell Chem Biol. 2016 Feb 8. pii: S2451-9456(16)30001-0. doi:, 10.1016/j.chembiol.2015.11.017. PMID:26877024[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ortega MA, Hao Y, Walker MC, Donadio S, Sosio M, Nair SK, van der Donk WA. Structure and tRNA Specificity of MibB, a Lantibiotic Dehydratase from Actinobacteria Involved in NAI-107 Biosynthesis. Cell Chem Biol. 2016 Feb 8. pii: S2451-9456(16)30001-0. doi:, 10.1016/j.chembiol.2015.11.017. PMID:26877024 doi:http://dx.doi.org/10.1016/j.chembiol.2015.11.017
