posted on 2021-07-01, 14:03authored byYing Duan, Marina Toplak, Anwei Hou, Nelson L. Brock, Jeroen S. Dickschat, Robin Teufel
Bacterial tropone
natural products such as tropolone, tropodithietic
acid, or the roseobacticides play crucial roles in various terrestrial
and marine symbiotic interactions as virulence factors, antibiotics,
algaecides, or quorum sensing signals. We now show that their poorly
understood biosynthesis depends on a shunt product from aerobic CoA-dependent
phenylacetic acid catabolism that is salvaged by the dedicated acyl-CoA
dehydrogenase-like flavoenzyme TdaE. Further characterization of TdaE
revealed an unanticipated complex catalysis, comprising substrate
dehydrogenation, noncanonical CoA-ester oxygenolysis, and final ring
epoxidation. The enzyme thereby functions as an archetypal flavoprotein
dioxygenase that incorporates both oxygen atoms from O2 into the substrate, most likely involving flavin-N5-peroxide and
flavin-N5-oxide species for consecutive CoA-ester cleavage and epoxidation,
respectively. The subsequent spontaneous decarboxylation of the reactive
enzyme product yields tropolone, which serves as a key virulence factor
in rice panicle blight caused by pathogenic edaphic Burkholderia
plantarii. Alternatively, the TdaE product is most likely
converted to more complex sulfur-containing secondary metabolites
such as tropodithietic acid from predominant marine Rhodobacteraceae (e.g., Phaeobacter inhibens).