Identification of Novel α-Pyrones from Conexibacter woesei Serving as Sulfate Shuttles

Abstract

Pyrones comprise a structurally diverse class of compounds. Although they are widespread in nature, their specific physiological functions remain unknown in most cases. We recently described that triketide pyrones mediate the sulfotransfer in caprazamycin biosynthesis. Herein, we report the identification of conexipyrones A−C, three previously unrecognized tetra-substituted α-pyrones, from the soil actinobacterium Conexibacter woesei. Insights into their biosynthesis via a type III polyketide synthase were obtained by feeding studies using isotope-enriched precursors. In vitro assays employing the genetically associated 3′-phosphoadenosine-5′-phosphosulfate (PAPS)-dependent sulfotransferase CwoeST revealed conexipyrones as the enzymes' genuine sulfate acceptor substrates. Furthermore, conexipyrones were determined to function as sulfate shuttles in a two-enzyme assay, because their sulfated derivatives were accepted as donor molecules by the PAPS-independent arylsulfate sulfotransferase (ASST) Cpz4 to yield sulfated caprazamycin intermediates.

Biosynthesis of 4-Acyl-5-aminoimidazole Alkaloids Featuring a New Friedel–Crafts Acyltransferase

“…These starting carbon atoms are considered to come from the metabolic pathways of valine, leucine, and isoleucine (Figure S10). − This inference also explains why the 13 C signal of C-10 in 4 was also enhanced when feeding 2- 13 C-labeled acetate, as acetyl-coenzyme A (acetyl-CoA) is one of the raw materials for the synthesis of isoleucine (Figures S9 and S10). These results strongly suggest that AAIAs are biosynthesized using precursors AIR and fatty acids from primary metabolism.…”