The identification and heterologous expression of the biosynthetic gene cluster encoding the antibiotic and anticancer agent marinomycin

Emily Abraham, Hannah Lawther, Yunpeng Wang, Joseph Scott Zarins-Tutt, Gerry Sann Rivera, Charles Chengcang Wu, Jack Connoly, Gordon John Florence, Matthias Onyebuchi Agbo, Hong Gao*, Rebecca Goss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.
Original languageEnglish
Article number117
Number of pages11
JournalBiomolecules
Volume14
Issue number1
DOIs
Publication statusPublished - 16 Jan 2024

Keywords

  • Antibiotic
  • VREF
  • MRSA
  • Melanoma
  • Synthetic biology
  • Biosynthetic gene cluster
  • Heterologous expression
  • Actinomycete
  • Marine natural product

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