Fig. 9: Proposed biosynthesis of Basidalin by BioPKS pipeline.

When prompted to suggest a biosynthesis route to basidalin, another therapeutic natural product whose biosynthetic origin also remains unknown, the BioPKS pipeline suggests a chimeric PKS design and three post-PKS modification steps to synthesize basidalin exactly. This chimeric PKS consists of 3 modules. The loading module and first extension module both use hydroxymalonyl-CoA as starter and extender units respectively while the final extension module uses malonyl-CoA as an extender unit. Again, an intramolecular cyclization reaction is chosen for offloading, and we note that RetroTide is able to synthesize the γ-lactone backbone of basidalin exactly. Subsequently, three post-PKS modification steps involving peroxygenase and aminotransferase enzymes can produce the target basidalin product. Source data are provided as a Source Data file.