Synthesis of (di)adenosine polyphosphates by non-ribosomal peptide synthetases (NRPS)

In response to nutritional stress conditions, Bacillus brevis produces the cyclodecapeptide antibiotic tyrocidine via tyrocidine synthetase, a multifu nctional non-ribosomal peptide synthetase. The ape-form of tyrocidine synth etase 1 forms adenosine (5 ' )tetraphospho(5 ' )adenosine, when incubated w ith MgATP(2-), amino acid and inorganic pyrophosphatase. The synthesis is a n intrinsic property of the adenylation domain, is strictly dependent upon the amino acid, and proceeds from a reverse reaction of adenylate formation involving a second ATP molecule. In the presence of tri- or tetrapolyphosp hate preferential synthesis of adenosine 5 ' -tetraphosphate and adenosine 5 ' -pentaphosphate occurs, respectively. A potential involvement of adenos ine (5 ')-n-phospho(5 ' )adenosine in the regulation of the biosynthetic pr ocess has been suggested. (C) 2001 Published by Elsevier Science B.V.