The identification and heterologous expression of the biosynthetic gene cluster encoding the antibiotic and anticancer agent marinomycin
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.
Citation
Abraham , E , Lawther , H , Wang , Y , Zarins-Tutt , J S , Rivera , G S , Wu , C C , Connoly , J , Florence , G J , Agbo , M O , Gao , H & Goss , R 2024 , ' The identification and heterologous expression of the biosynthetic gene cluster encoding the antibiotic and anticancer agent marinomycin ' , Biomolecules , vol. 14 , no. 1 , 117 . https://doi.org/10.3390/biom14010117
Publication
Biomolecules
Status
Peer reviewed
ISSN
2218-273XType
Journal article
Description
Funding: The authors acknowledge the support from the Marie Curie International Incoming Fellowship Grant within the 7th European Community Framework Programme (Grant No. 274110), the European Commission Seventh Framework Programme, Collaborative project “Bluegenics” (Grant No. 311848), EastBio studentship (Grant No. ACH7 – BDTP18), British Society for Antimicrobial Chemotherapy (Grant No. GA2016_005OS), and Equitable access to Quality Antibiotic Therapies in Africa (Grant No. EP/T020237/1).Collections
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