Biosynthesis of the proteasome inhibitor syringolin A: the ureido group joining two amino acids originates from bicarbonate

摘要: Syringolin A, an important virulence factor in the interaction of phytopathogenic bacterium Pseudomonas syringae pv. B728a with its host plant Phaseolus vulgaris (bean), was recently shown to irreversibly inhibit eukaryotic proteasomes by a novel mechanism. A is synthesized mixed non-ribosomal peptide synthetase/polyketide synthetase and consists tripeptide part including twelve-membered ring N-terminal valine that joined second via very unusual ureido group. Analysis sequence architecture syringolin gene cluster five open reading frames sylA-sylE allowed formulate biosynthesis model explained all structural features but left group unaccounted for.