Thiol Template Peptide Synthesis Systems in Bacteria and Fungi

Abstract

Publisher Summary This chapter discusses the thiol template peptide synthesis systems in bacteria and fungi. Peptide synthetase systems are defined as the arrangement of various amino-acid activation domains in the form of a multi-enzyme or a multi-enzyme complex. This has been shown by comparisons of various enzyme systems with their corresponding genes. The order of the various activation domains is mirrored in the sequence of the peptide synthesized in prokaryotes. Eukaryotic peptide synthetases always consist of a single polypeptide chain encoded by an intronless gene. This single polypeptide chain harbours the various adenylate formation domains, thioester, and additional modules necessary for the synthesis of a given product. In synthetases from fungi, the peptide is assembled by aminoadipyl-cysteinyl-D-valine synthase (ACVS), which has been isolated from a representative number of fungi and bacteria. Based on biochemical investigations in the cases of the enzymes from A. nidulans and S. clavuligerus and also considering the sequences of a number of ACVS genes, it is clear that this enzyme is composed of three peptide synthetase domains lying on one polypeptide chain of 420 kDa. Much progress in the enzymology of prokaryotic peptide synthetases has been achieved in the field of the acyl peptide lactone synthetases. Acyl peptide lactones consist of peptide lactone rings to which are attached aromatic or aliphatic side groups in an amide-like fashion.