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

doi:10.3390/biom14010117

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 journal › Article › peer-review

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 language	English
Article number	117
Number of pages	11
Journal	Biomolecules
Volume	14
Issue number	1
DOIs	https://doi.org/10.3390/biom14010117
Publication status	Published - 16 Jan 2024

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/biom14010117Licence: CC BY

Abraham-2024-Identification-and-heterologous-Biomolecules-14-00117-CCBY
Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).
Final published version, 2.03 MBLicence: CC BY

EQATA: EQATA: Equitable access to Quality Antibiotic Therapies in Africa
Florence, G. J. (PI) & Goss, R. (CoI)
EPSRC
1/04/20 → 31/03/22
Project: Standard
EU FP7 BlueGenics: BlueGenics
Goss, R. (PI)
European Commission
1/08/12 → 31/07/16
Project: Standard

The Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Antibiotic and Anticancer Agent Marinomycin (dataset)
Abraham, E. (Creator), Lawther, H. A. (Creator), Wang, Y. (Creator), Zarins-Tutt, J. S. (Creator), Rivera, G. S. (Creator), Chengcang Wu, C. (Creator), Connoly, J. (Creator), Florence, G. J. (Creator), Agbo, M. O. (Creator), Gao, H. (Creator) & Goss, R. (Creator), University of St Andrews, 5 Feb 2024
DOI: 10.17630/4cbdd552-b2b2-4304-a1ac-98029e926016
Dataset

File

Cite this

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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.",

keywords = "Antibiotic, VREF, MRSA, Melanoma, Synthetic biology, Biosynthetic gene cluster, Heterologous expression, Actinomycete, Marine natural product",

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

note = "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).",

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AU - Abraham, Emily

AU - Lawther, Hannah

AU - Wang, Yunpeng

AU - Zarins-Tutt, Joseph Scott

AU - Rivera, Gerry Sann

AU - Wu, Charles Chengcang

AU - Connoly, Jack

AU - Florence, Gordon John

AU - Agbo, Matthias Onyebuchi

AU - Gao, Hong

AU - Goss, Rebecca

N1 - 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).

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N2 - 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.

AB - 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.

KW - Antibiotic

KW - VREF

KW - MRSA

KW - Melanoma

KW - Synthetic biology

KW - Biosynthetic gene cluster

KW - Heterologous expression

KW - Actinomycete

KW - Marine natural product

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DO - 10.3390/biom14010117

M3 - Article

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SN - 2218-273X

VL - 14

JO - Biomolecules

JF - Biomolecules

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

Abstract

Keywords

UN SDGs

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Projects

EQATA: EQATA: Equitable access to Quality Antibiotic Therapies in Africa

EU FP7 BlueGenics: BlueGenics

Datasets

The Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Antibiotic and Anticancer Agent Marinomycin (dataset)

Cite this