TioS T-TE--a prototypical thioesterase responsible for cyclodimerization of the quinoline- and quinoxaline-type class of chromodepsipeptides.

The family of chromodepsipeptides constitutes a class of structurally related pseudosymmetrical peptidolactones and peptidothiolactones synthesized by nonribosomal peptide synthetases. The chromodepsipeptides, which are analogous to the extensively characterized echinomycin, attain their DNA-bisintercalating properties from chromophore moieties attached to the N-termini of the oligopeptide chain. Thiocoraline, a quinoline-substituted DNA-bisintercalator isolated from marine actinomycetes, is a two-fold symmetric octathiodepsipeptide currently undergoing preclinical trials phase II.

The iterative gramicidin s thioesterase catalyzes peptide ligation and cyclization.

Here, we present a comprehensive in vitro characterization of the excised iterative, bimodular PCP-TE of the gramicidin S synthetase GrsB, which is able to act both as a ligation and a cyclization catalyst. Using the native pentapeptidyl-thioester substrates, GrsB PCP-TE catalyzes the dimerization and subsequent formation of the decapeptide lactam gramicidin S. Interestingly, the detection of linear decapeptidyl-SNAC as an enzyme-dependent intermediate supports the iterative mechanism in vivo, in which two pentapeptides, one bound as an ester to the active site serine of the TE domain and the second bound as a thioester to the adjacent pan-PCP, are ligated to a decapeptidyl-pan-PCP that subsequently transferred to the adjacent TE domain and cyclized.