Tokyo Institute of Technology · Biochemistry, Genetics and Molecular Biology
Professor Po-Hsiang Wang's research lab specializes in microbial metabolism, particularly the anaerobic catabolism of steroids and xenobiotics. The lab investigates novel enzymatic pathways—such as the 2,3-seco and 9,10-seco pathways—involved in the degradation of testosterone, estrogens, and cholesterol under oxic and anoxic conditions. Using integrative approaches including (13)C-metabolomics, genome sequencing, and flux balance analysis, the lab uncovers microbial metabolic interdependencies and the roles of cofactors and enzyme promiscuity in environmental biodegradation. Their work bridges microbial physiology, environmental microbiology, and systems biology to understand how microbes drive the biogeochemical cycling of complex organic compounds.
Figures are computed from collected data and may differ slightly.
Steroid estrogens modulate physiology and development of vertebrates. Conversion of C<sub>19</sub> androgens into C<sub>18</sub> estrogens is thought to be an irreversible reaction. Here, we report a denitrifying <i>Denitratisoma</i> sp. strain DHT3 capable of catabolizing estrogens or androgens anaerobically. Strain DHT3 genome contains a polycistronic gene cluster, <i>emtABCD</i>, differentially transcribed under estrogen-fed conditions and predicted to encode a cobalamin-dependent methyltrans
The aerobic degradation of steroids by bacteria has been studied in some detail. In contrast, only little is known about the anaerobic steroid catabolism. Steroidobacter denitrificans can utilize testosterone under both oxic and anoxic conditions. By conducting metabolomic investigations, we demonstrated that S. denitrificans adopts the 9,10-seco-pathway to degrade testosterone under oxic conditions. This pathway depends on the use of oxygenases for oxygenolytic ring fission. Conversely, the det
The biodegradation of steroids is a crucial biochemical process mediated exclusively by bacteria. So far, information concerning the anoxic catabolic pathways of androgens is largely unknown, which has prevented many environmental investigations. In this work, we show that Sterolibacterium denitrificans DSMZ 13999 can anaerobically mineralize testosterone and some C19 androgens. By using a (13)C-metabolomics approach and monitoring the sequential appearance of the intermediates, we demonstrated
Two novel chlorinated alkane-respiring Dehalobacter restrictus strains CF and DCA were isolated from the same enrichment culture, ACT-3, and characterized. The closed genomes of these highly similar sister strains were previously assembled from metagenomic sequence data and annotated. The isolation of the strains enabled experimental verification of predicted annotations, particularly focusing on irregularities or predicted gaps in central metabolic pathways and cofactor biosynthesis. Similar to
Cholesterol is one of the most ubiquitous compounds in nature. The 9,10-seco-pathway for the aerobic degradation of cholesterol was established thirty years ago. This pathway is characterized by the extensive use of oxygen and oxygenases for substrate activation and ring fission. The classical pathway was the only catabolic pathway adopted by all studies on cholesterol-degrading bacteria. Sterolibacterium denitrificans can degrade cholesterol regardless of the presence of oxygen. Here, we aerobi
Microbes in ecosystems often develop coordinated metabolic interactions. Therefore, understanding metabolic interdependencies between microbes is critical to deciphering ecosystem function. In this study, we sought to deconstruct metabolic interdependencies in organohalide-respiring consortium ACT-3 containing Dehalobacter restrictus using a combination of metabolic modeling and experimental validation. D. restrictus possesses a complete set of genes for amino acid biosynthesis yet when grown in
Steroidal oestrogens are often accumulated in urban estuarine sediments worldwide at microgram per gram levels. These aromatic steroids have been classified as endocrine disruptors and group 1 carcinogens. Microbial degradation is a naturally occurring mechanism that mineralizes oestrogens in the biosphere; however, the corresponding genes in oestrogen-degrading actinobacteria remain unidentified. In this study, we identified a gene cluster encoding several putative oestrogen-degrading genes (ae
\Levels of progesterone, an endogenous female hormone, increase after ovulation; progesterone is crucial in the luteal phase to maintain successful pregnancy and prevent early miscarriage. Both endogenous and exogenous progesterone are recycled between the liver and gut; thus, the gut microbiota regulate host progesterone levels by inhibiting enterohepatic progesterone circulation. Our data indicated <i>Clostridium innocuum</i> as a major species involved in gut progesterone metabolism in women
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