Streptacidiphilus sp. PB12-B1b Genome sequencing. Streptacidiphilus sp. PB12-B1b

Actinobacteria are major sources of bioactive natural products in clinical and agricultural use. Over half of all antibiotics and many other bioactive compounds are produced by members of the Streptomycetaceae, and primarily by Streptomyces. Surprisingly, so far virtually no natural products have been described for its sister genus Streptacidiphilus. Here we describe a new family of spirotetronate polyketides, called streptaspironates, which are produced by Streptacidiphilus neutrinimicus, an obligate acidophilic actinobacterium isolated from decaying pine wood. While streptaspironate A (1) possesses conserved structural features, streptaspironate B (2) shows an unusual relative configuration, and offers the first ever example of a class I exo-spirotetronate. Furthermore, streptaspironates C (3) and D (4) have atypical truncations in their carbon skeleton, while streptaspironate D (4) features an unprecedented tricyclic methanobenzo[c]oxocin-11-one core. No bioactivity was detected for Streptaspironate B (2), despite its high structural resemblance to a potent antimicrobial/anticancer agent. Taken together, our work enriches the chemical space of natural products produced by Actinobacteria, and shows the potential of the genus Streptacidiphilus as producers of new compounds.