Improving the production of 22-hydroxy-23,24-bisnorchol-4-ene-3-one from sterols in Mycobacterium neoaurum by increasing cell permeability and modifying multiple genes

Microbial Cell Factories
Liang-Bin XiongDong-Zhi Wei

Abstract

The strategy of modifying the sterol catabolism pathway in mycobacteria has been adopted to produce steroidal pharmaceutical intermediates, such as 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC), which is used to synthesize various steroids in the industry. However, the productivity is not desirable due to some inherent problems, including the unsatisfactory uptake rate and the low metabolic efficiency of sterols. The compact cell envelope of mycobacteria is a main barrier for the uptake of sterols. In this study, a combined strategy of improving the cell envelope permeability as well as the intracellular sterol metabolism efficiency was investigated to increase the productivity of 4-HBC. MmpL3, encoding a transmembrane transporter of trehalose monomycolate, is an important gene influencing the assembly of mycobacterial cell envelope. The disruption of mmpL3 in Mycobacterium neoaurum ATCC 25795 significantly enhanced the cell permeability by 23.4% and the consumption capacity of sterols by 15.6%. Therefore, the inactivation of mmpL3 was performed in a 4-HBC-producing strain derived from the wild type M. neoaurum and the 4-HBC production in the engineered strain was increased by 24.7%. Subsequently, to enhance the metabolic eff...Continue Reading

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Citations

Nov 16, 2018·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Rahul PalZeeshan Fatima
Jun 6, 2018·Frontiers in Microbiology·Lorena Fernández-CabezónJosé L García
Mar 5, 2021·Microbial Biotechnology·Carmen Felpeto-SanteroJosé Luis García
Apr 7, 2021·Biotechnology Advances·Ali Rohman, Bauke W Dijkstra

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Datasets Mentioned

BETA
AMO04272.1
AHC23578.1

Methods Mentioned

BETA
genetic modifications
PCR
Fluorescence

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