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Building Chemical Tools From The Indolmycin Biosynthetic Genes

Date: 
Thursday, November 21, 2019 - 18:30 to 19:30
Speaker: 
Elesha Hoffarth
Affiliation: 
Department of Chemistry, The University of British Columbia
Event Category: 
CBDG - Chemical Biology Discussion Group
Location: 
Chemistry D300

Abstract:

Indolmycin is a natural antibiotic from Streptomyces griseus whose biosynthesis can provide tools for both therapeutic and biocatalyst development. The cost of producing indolmycin has limited the production and testing of derivatives for bioactivity. The indolmycin biosynthetic genes and a promiscuous tryptophanyl-tRNA synthetase are used to semi-synthetically produce indolmycin derivatives from substituted indoles. This provides a combinatorial approach to access a variety of derivatives for antimicrobial testing. Additionally, the indolmycin biosynthetic pathway contains a unique oxygen and PLP-dependent enzyme catalyzing two dehydrogenation reactions on arginine through a highly enigmatic mechanism. The reactivity of this enzyme is explored through biochemical assays, X-ray crystallography and mutagenesis.