Abstract
ABSTRACTComamonas testosteroniis one of the representative aerobic steroid-degrading bacterium. We previously revealed the mechanism of steroidal A,B,C,D-ring degradation byC. testosteroniTA441. The corresponding genes are located in two clusters at both ends of a mega-cluster of steroid degradation genes. ORF7 and ORF6 are the only two genes in these clusters, whose function has not been determined. Here, we characterized ORF7 as encoding the dehydrase responsible for converting the C12β hydroxyl group to the C10(12) double bond on the C-ring (SteC), and ORF6 as encoding the hydrogenase responsible for converting the C10(12) double bond to a single bond (SteD). SteA and SteB, encoded just upstream of SteC and SteD, are in charge of oxidizing the C12α hydroxyl group to a ketone group, and of reducing the latter to the C12β hydroxyl group, respectively. Therefore, the C12α hydroxyl group in steroids is removed with SteABCD via the C12 ketone and C12β hydroxyl groups. Given the functional characterization of ORF6 and ORF7, we disclose the entire pathway of steroidal A,B,C,D-ring breakdown byC. testosteroniTA441.IMPORTANCEStudies on bacterial steroid degradation were initiated more than 50 years ago, primarily to obtain materials for steroid drugs. Now, their implications for the environment and humans, especially in relation to the infection and the brain-gut-microbiota axis, are attracting increasing attention.Comamonas testosteroniTA441 is the leading model of bacterial aerobic steroid degradation with the ability to break down cholic acid, the main component of bile acids. Bile acids are known for their variety of physiological activities according as their substituent group(s). In this study, we identified and functionally characterized the genes for removal of C12 hydroxyl groups and provide a comprehensive summary of the entire A,B,C,D-ring degradation pathway byC. testosteroniTA441 as the representable bacterial aerobic degradation process of the steroid core structure.
Publisher
Cold Spring Harbor Laboratory
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