Affiliation:
1. Department of Chemistry & BSRC, University of St. Andrews, St. Andrews KY16 9ST, UK
2. Intact Genomics, St. Louis, MO 63132, USA
Abstract
With the rise in antimicrobial resistance, there is an urgent need for new classes of antibiotic with which to treat infectious disease. Marinomycin, a polyene antibiotic from a marine microbe, has been shown capable of killing methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF), as well as having promising activity against melanoma. An attractive solution to the photoprotection of this antibiotic has been demonstrated. Here, we report the identification and analysis of the marinomycin biosynthetic gene cluster (BGC), and the biosynthetic assembly of the macrolide. The marinomycin BGC presents a challenge in heterologous expression due to its large size and high GC content, rendering the cluster prone to rearrangement. We demonstrate the transformation of Streptomyces lividans using a construct containing the cluster, and the heterologous expression of the encoded biosynthetic machinery and production of marinomycin B.
Funder
Marie Curie International Incoming Fellowship Grant
European Commission
EastBio
British Society for Antimicrobial Chemotherapy
Equitable access to Quality Antibiotic Therapies in Africa
Subject
Molecular Biology,Biochemistry
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