Irina recently presented a non-ribosomal peptide synthetase-derived thioesterase which served to cleave a completed linear polypeptide chain from a solid-phase synthetic assembly line and induce macrocyclization to yield the desired macrocycle. This article highlights an unusual thioesterase action mediated by two independent thioesterase domains, where one is responsible for substrate cleavage and the other for macrocyclization. This interesting alternative highlights the importance of correct thioesterase activity, in that different thioesterases with distinct activities may be necessary for macrocyclization fidelity.
Interesting paper! I think though only the first TE is required for macrocyclization. The second TE is used as an editing enzyme to simply hydrolyze PCP's that are primed with the wrong peptide?
ReplyDeleteRereading Characterization of LybB Thioesterase Activities I see TE 1 is the only TE necessary for macrocyclization. As Dr. Williams points out, TE 2 instead helps maintain fidelity of the substrate peptide.
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