Excised macrocyclization

TE-catalyzed cyclization is not limited to the synthesis of macrocyclic peptides by catalyzing the formation of aC N bond. These enzymes are also responsible for the cyclization of NRP depsipeptide and PK lactone. Indeed, a di-domain excised from fengycin synthase was... 

Figure 7 Chemoenzymatic synthesis of macroiactams cataiyzed by Tyc TE. The excised Tyc TE is capabie to produce tyrocidine A (14) with the linear decapeptide NAC thioester or PEGA resin (in blue) with a biomimetic linker. Tyc TE tolerates various modifications to the residues in the rectangle box. However, o-Phe, i-Orn, and i-Leu (in red) are required in all substrates. With modified substrates, Tyc TE generates both macrocyclic peptides with 6-14 amino acids and tyrocidine analogues with different sugar moieties attached to position 4, 5, 6, and 7.

KR), dehydratase (DH), and enol reductase (ER) domains while docked at the ACP. Once fully processed, the extended chain is passed to the KS of the subsequent module by a transthioesterification reaction. The process is repeated, leading to the final module where the product is generally excised via hydrolysis or thioesterase (TE) mediated macrocyclization. 

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