Microaerophilic conditions cue secondary metabolite variability in a marine-derived Streptomyces strain

Members of the actinomycete genus Streptomyces are immotile filamentous bacteria that are generally considered obligate aerobes. They have primarily been isolated from highly heterogeneous environments, including soils and marine sediments, yet little is known about how these organisms grow or survive in microaerophilic conditions. Here we investigate the role of secondary metabolism in streptomycete adaptation to low oxygen environments by tracking secondary metabolite production by a marine Streptomyces strain, CNQ-525, in continuous culture as oxygen was lowered. We found clear evidence for a shift in secondary metabolism that was linked to the napyradiomycin biosynthesis pathway, which under reduced oxygen produced a significantly higher amount of a truncated pathway product, the pigmented meroterpenoid precursor molecule 8-amino-flaviolin. Napyradiomycin and 8-amino-flaviolin possess fundamentally different solubility and bioactivity characteristics, which suggests that depending on local environmental conditions, a single biosynthetic pathway can produce distinct products for different functions. Because molecules similar to 8-amino-flaviolin are known to function as endogenous electron shuttles, we tested the ability of strain CNQ-525 to reduce an insoluble electron acceptor. In a plate assay, this strain was able to reduce Mn(IV) via an indirect mechanism. Electrochemical studies of purified 8-amino-flaviolin confirmed that this molecule is redox-active. This study provides some of the first evidence that secondary metabolism may play a role in Streptomyces adaptation to microaerophilic environments.