The Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Antibiotic and Anticancer Agent Marinomycin
2024
Emily Abraham | Hannah A. Lawther | Yunpeng Wang | Joseph S. Zarins-Tutt | Gerry Sann Rivera | Chengcang Wu | Jack A. Connolly | Gordon Florence | Matthias Agbo | Hong Gao | Rebecca J. M. Goss
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 <i>Staphylococcus aureus</i> (MRSA) and vancomycin-resistant <i>Enterococcus faecium</i> (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 <i>Streptomyces lividans</i> using a construct containing the cluster, and the heterologous expression of the encoded biosynthetic machinery and production of marinomycin B.
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