A Flavoprotein Dioxygenase Steers Bacterial Tropone Biosynthesis via Coenzyme A-Ester Oxygenolysis and Ring Epoxidation

• DOI: 10.1021/jacs.1c04996
• Publication Date: 2021-07-01T13:55:24Z
• Authors: Ying Duan; Marina Toplak; Anwei Hou; Nelson L. Brock; Jeroen S. Dickschat; Robin Teufel
• Keywords: Flavoprotein; Decarboxylation; Dioxygenase; Oxidative decarboxylation; Hydroxylation

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