The biosynthetic system for the production of a non-ribosomal peptide operates nucleic acid-free at the protein level. The specific condensation of amino acids and related carboxyl containing compounds is directed by protein templates, and each biosynthetic step generally requires a protein module. A minimal configuration consists of an adenylation domain for amino acid activation, a thiolation domain for transfer of activated intermediates, and a condensation domain.
Domains and modules are assembled at the gene level into gene clusters, which are translated into multifunctional proteins or multi-enzyme complexes, and post-translationally modified by addition of 4'-phosphopantetheine to the thiolation domain [Welker06].
Since a minimal module requires 3-3.5 kbp of genetic sequence, and since most non-ribosomal peptide synthetases (NRPSs) consist of several such modules, some NRPS genes are the largest known genes [Finking04].
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493