A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism

CYP102A1 (BM3) is a catalytically self-sufficient flavocytochrome fusion protein isolated from <i>Bacillus megaterium</i>, which displays similar metabolic capabilities to many drug-metabolizing human P450 isoforms. BM3′s high catalytic efficiency, ease of production and malleable active...

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Autores principales:	Sian Thistlethwaite, Laura N. Jeffreys, Hazel M. Girvan, Kirsty J. McLean, Andrew W. Munro
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	CYP102A1 P450 BM3 drug metabolism cytochromes P450 P450 engineering biocatalysis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5d9b5c24683a4f389d4469fba5f9a5c4
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spelling	oai:doaj.org-article:5d9b5c24683a4f389d4469fba5f9a5c42021-11-11T16:51:15ZA Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism10.3390/ijms2221113801422-00671661-6596https://doaj.org/article/5d9b5c24683a4f389d4469fba5f9a5c42021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11380https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067CYP102A1 (BM3) is a catalytically self-sufficient flavocytochrome fusion protein isolated from <i>Bacillus megaterium</i>, which displays similar metabolic capabilities to many drug-metabolizing human P450 isoforms. BM3′s high catalytic efficiency, ease of production and malleable active site makes the enzyme a desirable tool in the production of small molecule metabolites, especially for compounds that exhibit drug-like chemical properties. The engineering of select key residues within the BM3 active site vastly expands the catalytic repertoire, generating variants which can perform a range of modifications. This provides an attractive alternative route to the production of valuable compounds that are often laborious to synthesize via traditional organic means. Extensive studies have been conducted with the aim of engineering BM3 to expand metabolite production towards a comprehensive range of drug-like compounds, with many key examples found both in the literature and in the wider industrial bioproduction setting of desirable oxy-metabolite production by both wild-type BM3 and related variants. This review covers the past and current research on the engineering of BM3 to produce drug metabolites and highlights its crucial role in the future of biosynthetic pharmaceutical production.Sian ThistlethwaiteLaura N. JeffreysHazel M. GirvanKirsty J. McLeanAndrew W. MunroMDPI AGarticleCYP102A1P450 BM3drug metabolismcytochromes P450P450 engineeringbiocatalysisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11380, p 11380 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CYP102A1 P450 BM3 drug metabolism cytochromes P450 P450 engineering biocatalysis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	CYP102A1 P450 BM3 drug metabolism cytochromes P450 P450 engineering biocatalysis Biology (General) QH301-705.5 Chemistry QD1-999 Sian Thistlethwaite Laura N. Jeffreys Hazel M. Girvan Kirsty J. McLean Andrew W. Munro A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism
description	CYP102A1 (BM3) is a catalytically self-sufficient flavocytochrome fusion protein isolated from <i>Bacillus megaterium</i>, which displays similar metabolic capabilities to many drug-metabolizing human P450 isoforms. BM3′s high catalytic efficiency, ease of production and malleable active site makes the enzyme a desirable tool in the production of small molecule metabolites, especially for compounds that exhibit drug-like chemical properties. The engineering of select key residues within the BM3 active site vastly expands the catalytic repertoire, generating variants which can perform a range of modifications. This provides an attractive alternative route to the production of valuable compounds that are often laborious to synthesize via traditional organic means. Extensive studies have been conducted with the aim of engineering BM3 to expand metabolite production towards a comprehensive range of drug-like compounds, with many key examples found both in the literature and in the wider industrial bioproduction setting of desirable oxy-metabolite production by both wild-type BM3 and related variants. This review covers the past and current research on the engineering of BM3 to produce drug metabolites and highlights its crucial role in the future of biosynthetic pharmaceutical production.
format	article
author	Sian Thistlethwaite Laura N. Jeffreys Hazel M. Girvan Kirsty J. McLean Andrew W. Munro
author_facet	Sian Thistlethwaite Laura N. Jeffreys Hazel M. Girvan Kirsty J. McLean Andrew W. Munro
author_sort	Sian Thistlethwaite
title	A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism
title_short	A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism
title_full	A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism
title_fullStr	A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism
title_full_unstemmed	A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism
title_sort	promiscuous bacterial p450: the unparalleled diversity of bm3 in pharmaceutical metabolism
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5d9b5c24683a4f389d4469fba5f9a5c4
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A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism

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