Phosphitispora sp. TUW77 Genome sequencing. Phosphitispora sp. TUW77

Although sex hormones, namely androgen and estrogen, were thought to produced exclusively by vertebrates and may appear after the Cambrian explosion, sterols can be biosynthesized under microaerobic conditions and are proposed to appear on earth 2.3 billion years ago. A variety of aerobic and anaerobic prokaryotes can degrade the side-chain of sterols through beta-oxidation, remaining androgens as end products. One can thus envisage that androgens could appear soon after sterols were produced. Here, we report that strain TUW77, an acetogen isolated from the gut of great blue-spotted mudskipper (Boleophthalmus pectinirostris), can transform testosterone into estrone and 17beta-estradiol through the Wood-Ljundahl pathway; the resulting androgenic C-19 methyl group is used as carbon and electron donors for bacterial growth. Physiological exams indicated that the strain TUW77 exclusively grows with testosterone, with estrogens as extracellular end products. The strain TUW77 genome contains two copies of a polycistronic gene cluster, aetABC (Anaerobic EsTrogenesis), which respectively encode the MT1, CoP, and MT2 components of a cobalamin-dependent methyltransferase and were highly expressed under testosterone-fed conditions and. Consistently, we observed the apparent production of AetABC in the testosterone-grown bacterial cells. Surprisingly, the primary structures of the MT1 (AetA) and CoP (AetB) components are most similar to the characterized EmtAB from the denitrifying Denitratisoma sp. strain DHT3 capable of anaerobically transforming estrogen into androgen (the reverse reaction). The identification of the cobalamin-dependent estrogenesis in acetogens represents an unprecedented metabolic link between steroid hormones biosynthesis and ancient C1 metabolism through the Wood-Ljundahl pathway.