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Mechanistic Probes for the Epimerization Domain of Nonribosomal Peptide Synthetases.

ABSTRACT: Nonribosomal peptide synthetases (NRPSs) are responsible for the synthesis of a variety of bioactive natural products with clinical and economic significance. Interestingly, these large multimodular enzyme machineries incorporate nonproteinogenic d-amino acids through the use of auxiliary epimerization domains, converting l-amino acids into d-amino acids that impart into the resulting natural products unique bioactivity and resistance to proteases. Due to the large and complex nature of NRPSs, several questions remain unanswered about the mechanism of the catalytic domain reactions. We have investigated the use of mechanism-based crosslinkers to probe the mechanism of an epimerization domain in gramicidin?S biosynthesis. In addition, MD simulations were performed, showcasing the possible roles of catalytic residues within the epimerization domain.

SUBMITTER: Kim WE

PROVIDER: S-EPMC6632073 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Mechanistic Probes for the Epimerization Domain of Nonribosomal Peptide Synthetases.

Kim Woojoo E WE Patel Ashay A Hur Gene H GH Tufar Peter P Wuo Michael G MG McCammon J Andrew JA Burkart Michael D MD

Chembiochem : a European journal of chemical biology 20181109 2

Nonribosomal peptide synthetases (NRPSs) are responsible for the synthesis of a variety of bioactive natural products with clinical and economic significance. Interestingly, these large multimodular enzyme machineries incorporate nonproteinogenic d-amino acids through the use of auxiliary epimerization domains, converting l-amino acids into d-amino acids that impart into the resulting natural products unique bioactivity and resistance to proteases. Due to the large and complex nature of NRPSs, s ...[more]

PMID: 30194895

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