RESUMO
The structure of the sidechain crosslinked Tyr-Leu-Trp peptide produced by the biarylitide crosslinking cytochrome P450Blt from Micromonospora sp. MW-13 has been reanalysed by a series of NMR, computational and isotope labelling experiments and shown to contain a C-N rather than a C-O bond. Additional inâ vivo experiments using such a modified peptide show there is a general tolerance of biarylitide crosslinking P450 enzymes for histidine to tryptophan mutations within their minimal peptide substrate sequences despite the lack of such residues noted in natural biarylitide gene clusters. This work further highlights the impressive ability of P450s from biarylitide biosynthesis pathways to act as biocatalysts for the formation of a range of sidechain crosslinked tripeptides.
Assuntos
Sistema Enzimático do Citocromo P-450 , Peptídeos Cíclicos , Triptofano , Triptofano/química , Triptofano/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/química , Peptídeos Cíclicos/química , Micromonospora/química , Micromonospora/metabolismo , Reagentes de Ligações Cruzadas/química , BiocatáliseRESUMO
As part of our search for natural products active against the JNK3 kinase, two novel, charged benzylisoquinolines, latifolian A (1) and latifolian B (2), were isolated from the stem bark of the Papua New Guinean vine Gnetum latifolium. The planar structures were determined through detailed 2D NMR analysis. The relative configurations were assigned after examination of the ROESY data and through detailed molecular modeling studies.