Interrogation of Benzomalvin Biosynthesis Using Fungal Artificial Chromosomes with Metabolomic Scoring (FAC-MS): Discovery of a Benzodiazepine Synthase Activity.

ABSTRACT: The benzodiazepine benzomalvin A/D is a fungally derived specialized metabolite and inhibitor of the substance P receptor NK1, biosynthesized by a three-gene nonribosomal peptide synthetase cluster. Here, we utilize fungal artificial chromosomes with metabolomic scoring (FAC-MS) to perform molecular genetic pathway dissection and targeted metabolomics analysis to assign the in vivo role of each domain in the benzomalvin biosynthetic pathway. The use of FAC-MS identified the terminal cyclizing condensation domain as BenY-C_T and the internal C-domains as BenZ-C₁ and BenZ-C₂. Unexpectedly, we also uncovered evidence suggesting BenY-C_T or a yet to be identified protein mediates benzodiazepine formation, representing the first reported benzodiazepine

SUBMITTER: Clevenger KD 

PROVIDER: S-EPMC5997561 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature