Production of 11α‐hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis

Summary 11α‐hydroxylated steroid synthons are one of the most important commercially pharmaceutical intermediates used for the production of contraceptive drugs and glucocorticoids. These compounds are currently produced by biotransformation using fungal strains in two sequential fermentation steps....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Carmen Felpeto‐Santero, Beatriz Galán, José Luis García
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/1e0594d31c574524a6ec9f61dde765e4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1e0594d31c574524a6ec9f61dde765e4
record_format	dspace
spelling	oai:doaj.org-article:1e0594d31c574524a6ec9f61dde765e42021-11-18T15:39:53ZProduction of 11α‐hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis1751-791510.1111/1751-7915.13735https://doaj.org/article/1e0594d31c574524a6ec9f61dde765e42021-11-01T00:00:00Zhttps://doi.org/10.1111/1751-7915.13735https://doaj.org/toc/1751-7915Summary 11α‐hydroxylated steroid synthons are one of the most important commercially pharmaceutical intermediates used for the production of contraceptive drugs and glucocorticoids. These compounds are currently produced by biotransformation using fungal strains in two sequential fermentation steps. In this work, we have developed by a rational design new recombinant bacteria able to produce 11α‐hydroxylated synthons in a single fermentation step using cholesterol (CHO) or phytosterols (PHYTO) as feedstock. We have designed a synthetic operon expressing the 11α‐hydroxylating enzymes from the fungus Rhizopus oryzae that was cloned into engineered mutant strains of Mycolicibacterium smegmatis that were previously created to produce 4‐androstene‐3,17‐dione (AD), 1,4‐androstadiene‐3,17‐dione (ADD) from sterols. The introduction of the fungal synthetic operon in these modified bacterial chassis has allowed producing for the first time 11αOH‐AD and 11αOH‐ADD with high yields directly from sterols in a single fermentation step. Remarkably, the enzymes of sterol catabolic pathway from M. smegmatis recognized the 11α‐hydroxylated intermediates as alternative substrates and were able to efficiently funnel sterols to the desired hydroxylated end‐products.Carmen Felpeto‐SanteroBeatriz GalánJosé Luis GarcíaWileyarticleBiotechnologyTP248.13-248.65ENMicrobial Biotechnology, Vol 14, Iss 6, Pp 2514-2524 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biotechnology TP248.13-248.65
spellingShingle	Biotechnology TP248.13-248.65 Carmen Felpeto‐Santero Beatriz Galán José Luis García Production of 11α‐hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis
description	Summary 11α‐hydroxylated steroid synthons are one of the most important commercially pharmaceutical intermediates used for the production of contraceptive drugs and glucocorticoids. These compounds are currently produced by biotransformation using fungal strains in two sequential fermentation steps. In this work, we have developed by a rational design new recombinant bacteria able to produce 11α‐hydroxylated synthons in a single fermentation step using cholesterol (CHO) or phytosterols (PHYTO) as feedstock. We have designed a synthetic operon expressing the 11α‐hydroxylating enzymes from the fungus Rhizopus oryzae that was cloned into engineered mutant strains of Mycolicibacterium smegmatis that were previously created to produce 4‐androstene‐3,17‐dione (AD), 1,4‐androstadiene‐3,17‐dione (ADD) from sterols. The introduction of the fungal synthetic operon in these modified bacterial chassis has allowed producing for the first time 11αOH‐AD and 11αOH‐ADD with high yields directly from sterols in a single fermentation step. Remarkably, the enzymes of sterol catabolic pathway from M. smegmatis recognized the 11α‐hydroxylated intermediates as alternative substrates and were able to efficiently funnel sterols to the desired hydroxylated end‐products.
format	article
author	Carmen Felpeto‐Santero Beatriz Galán José Luis García
author_facet	Carmen Felpeto‐Santero Beatriz Galán José Luis García
author_sort	Carmen Felpeto‐Santero
title	Production of 11α‐hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis
title_short	Production of 11α‐hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis
title_full	Production of 11α‐hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis
title_fullStr	Production of 11α‐hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis
title_full_unstemmed	Production of 11α‐hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis
title_sort	production of 11α‐hydroxysteroids from sterols in a single fermentation step by mycolicibacterium smegmatis
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/1e0594d31c574524a6ec9f61dde765e4
work_keys_str_mv	AT carmenfelpetosantero productionof11ahydroxysteroidsfromsterolsinasinglefermentationstepbymycolicibacteriumsmegmatis AT beatrizgalan productionof11ahydroxysteroidsfromsterolsinasinglefermentationstepbymycolicibacteriumsmegmatis AT joseluisgarcia productionof11ahydroxysteroidsfromsterolsinasinglefermentationstepbymycolicibacteriumsmegmatis
_version_	1718420772196712448

Production of 11α‐hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis

Ejemplares similares