Metabolic Adaptation of Mycobacterium neoaurum ATCC 25795 in the Catabolism of Sterols for Producing Important Steroid Intermediates

摘要

To understand the adaptation of Mycobacterium neoaurum ATCC25795 (Mn) in sterol catabolism and steroid production, we used integrated transcriptome and proteome analysis to identify the biochemical pathways utilized in this process. Metabolic alterations during sterol catabolism center on propionyl-CoA pools. Generally, enhanced pathways for metabolizing propionyl-CoA were found in Mn, which were tightly coordinated with cell-envelope biosynthesis. The cells responded to sterol substrates and toxic steroid products by changing the composition of the cell envelope. This adaptive mechanism allowed Mn to use minimally water-soluble sterol as a carbon source. Several putative efflux proteins were found to be induced in Mn. They probably transported products to the extracellular environment, protecting the cells against high intracellular levels of toxic intermediates, inhibition of which also influenced sterol uptake. The work provided various targets for rational engineering of robust Mn with powerful sterol-uptake capacity and strong tolerance to toxic products for the steroid industry.