Amino acid activation and polymerization at modular multienzymes in nonribosomal peptide biosynthesis

Summary The biosynthesis of microbial bioactive peptides is accomplished nonribosomally by large multifunctional enzymes consisting of linearly arranged building blocks of 1,000–1,500 amino acid residues. Each of these units acts as an independent enzyme which catalyzes the selection, activation, and in some cases modification (epimerization, N-methylation) of its cognate amino acid, as well as the elongation of the peptide product. The specific linkage of amino acid activating modules upon such polyenzymes defines the sequence of the peptide product. A series of functional domains could be identified upon an amino acid activating module which are involved in the sequential reactions in nonribosomal peptide biosynthesis.Abbrevations aaRS aminoacyl tRNA synthetase - GS1 gramicidin S synthetase 1 (phenylalanine racemase) - GS2 gramicidin S synthetase 2 - TY1 and 2 tyrocidine synthetase 1 and 2 - ACV -(l--aminoadipyl)-l-cysteinyl-d-valine] - FITC fluorescein 5-isothiocyanate - FAB-, ESI-MS fast atom bombardment-, electrospray ionization-mass spectrometry - Pan 4-phosphopantetheine - NMR nuclear magnetic resonance - ACP acyl carrier protein - SAM S-adenosyl-l-methionine - CM carboxy-methyl - NES Nethylsuccinimido