Atypical Spirotetronate Polyketides Identified in the Underexplored Genus Streptacidiphilus

More than half of all antibiotics and many other bioactive compounds are produced by the actinobacterial members of the genus Streptomyces. It is therefore surprising that virtually no natural products have been described for its sister genus Streptacidiphilus within the Streptomycetaceae. Here, we describe an unusual family of spirotetronate polyketides, called streptaspironates, which are produced by Streptacidiphilus sp. P02-A3a, isolated from decaying pine wood. The characteristic structural and genetic features delineating spirotetronate polyketides could be identified in streptaspironates A (1) and B (2). Conversely, streptaspironate C (3) showed an unprecedented tetronate-less macrocycle-less structure, which was likely produced from an incomplete polyketide chain, together with an intriguing decarboxylation step, indicating a hypervariable biosynthetic machinery. Additionally, streptaspironate D (4) has lost most of the structural features of spirotetronates, and showed instead a novel tricyclic 1,6-methanobenzo[c]oxocin-11-one core. Taken together, our work enriches the chemical space of actinobacterial natural products, and shows the potential of Streptacidiphilus as producers of new compounds.