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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.

SUBMITTER: Abraham E 

PROVIDER: S-EPMC10813093 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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The Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Antibiotic and Anticancer Agent Marinomycin.

Abraham Emily E   Lawther Hannah A HA   Wang Yunpeng Y   Zarins-Tutt Joseph S JS   Rivera Gerry Sann GS   Wu Chengcang C   Connolly Jack A JA   Florence Gordon G   Agbo Matthias M   Gao Hong H   Goss Rebecca J M RJM  

Biomolecules 20240116 1


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 r  ...[more]

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