Identification of the aldolase responsible for the production of 22‐hydroxy‐23,24‐bisnorchol‐4‐ene‐3‐one from natural sterols in Mycolicibacterium smegmatis

Author:

Hernández‐Fernández Gabriel1,Acedos Miguel G.1,García José L.1ORCID,Galán Beatriz1ORCID

Affiliation:

1. Department of Microbial and Plant Biotechnology Centro de Investigaciones Biológicas Margarita Salas (CSIC) Madrid Spain

Abstract

AbstractMycobacterial mutants blocked in ring degradation constructed to achieve C19 synthons production, also accumulate by‐products such as C22 intermediates throughout an alternative pathway reducing the production yields and complicating the downstream purification processing of final products. In this work, we have identified the MSMEG_6561 gene, encoding an aldolase responsible for the transformation of 22‐hydroxy‐3‐oxo‐cholest‐4‐ene‐24‐carboxyl‐CoA (22‐OH‐BCN‐CoA) into the 22‐hydroxy‐23,24‐bisnorchol‐4‐ene‐3‐one (4‐HBC) precursor (20S)‐3‐oxopregn‐4‐ene‐20‐carboxaldehyde (3‐OPA). The deletion of this gene increases the production yield of the C‐19 steroidal synthon 4‐androstene‐3,17‐dione (AD) from natural sterols, avoiding the production of 4‐HBC as by‐product and the drawbacks in the AD purification. The molar yield of AD production using the MS6039‐5941‐6561 triple mutant strain was checked in flasks and bioreactor improving very significantly compared with the previously described MS6039‐5941 strain.

Funder

Comunidad de Madrid

Ministerio de Ciencia e Innovación

Ministerio de Economía y Competitividad

Publisher

Wiley

Subject

Applied Microbiology and Biotechnology,Biochemistry,Bioengineering,Biotechnology

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