Organization of the phormidolide pathway. The pathway, identified from the genome of a Leptolyngbya sp., has many of the reported hallmarks of a trans-AT PKS system, including (1) discrete AT enzymes upstream of the PKS megasynthase architecture; (2) tandem ACP domains; (3) split modules; (4) non-elongating KS0 domains; (5) embedded ECH pairs and (6) HCS cassette. ACPS acyl carrier protein synthase, oMT O-methyltransferase, FkbH FkbH-phosphatase, ATd docking acyltransferase, KS0 non-elongating ketosynthase, PS pyran synthase, C NRPS-like condensation domain, Hal halogenase, Hydro hydrolase, 4′PP 4′-phosphopantetheine, FACL Fatty Acid CoA Ligase, HCS HMG-CoA synthase, PEP phosphoenolpyruvate