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Structure and tRNA Specificity of MibB, a Lantibiotic Dehydratase from Actinobacteria Involved in NAI-107 Biosynthesis.


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.

SUBMITTER: Ortega MA 

PROVIDER: S-EPMC4798866 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Structure and tRNA Specificity of MibB, a Lantibiotic Dehydratase from Actinobacteria Involved in NAI-107 Biosynthesis.

Ortega Manuel A MA   Hao Yue Y   Walker Mark C MC   Donadio Stefano S   Sosio Margherita M   Nair Satish K SK   van der Donk Wilfred A WA  

Cell chemical biology 20160211 3


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 lant  ...[more]

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