複数のアデニル酸形成酵素がDPOクオラムセンシング自己誘導体の生合成に寄与する

Bacteria use a process of chemical communication called quorum sensing to regulate group behaviors. Quorum sensing relies on the synthesis, release, and detection of signal molecules called autoinducers that accumulate with increasing cell density. The pathogen Vibrio cholerae makes and detects three autoinducers which together, regulate genes required for group behaviors including virulence and biofilm formation. Two autoinducers are produced by dedicated autoinducer synthases that employ S-adenosyl methionine as a substrate. The third autoinducer, 3,5-dimethylpyrazin-2-ol (DPO), is produced from threonine and alanine. The threonine dehydrogenase (Tdh) enzyme oxidizes l-threonine to 2-amino-3-ketobutyric acid, which spontaneously decarboxylates to aminoacetone. Here, we define the steps required to convert aminoacetone and alanine into DPO. We show that diverse adenylate-forming enzymes can condense ATP and d- or l-alanine to form alanyl-adenylate, the necessary intermediate in DPO biosynthesis. Upon release, alanyl-adenylate spontaneously condenses with aminoacetone to form N-alanyl-aminoacetone, which cyclizes to form DPO. We propose that DPO is distinct from other autoinducers in that there is apparently no dedicated synthase. Rather, a collection of enzymes contribute to the production of this quorum-sensing autoinducer.