The biarylitides: understanding the structure and biosynthesis of a fascinating class of Cytochrome P450 modified RiPP natural products.

The biarylitides are a recently discovered class of RiPP natural products that are fascinating both from the small size of the core peptides as well as the diversity of peptide crosslinking exhibited by the cytochrome P450 enzymes found in these systems. In this review, we address the discovery and biosynthetic diversity of these systems and discuss the methods and challenges of analysing the structures of these constrained cyclic peptides. We also discuss the structures of the P450 enzymes involved in these pathways and address the potential for alternate catalytic outcomes and activities as seen most recently with the inclusion of biarylitide related enzymes within rufomycin biosynthesis.

Loss of fluorine during crosslinking by the biarylitide P450 proceeds due to restricted peptide orientation.

The biarylitide crosslinking enzyme P450 can perform crosslinking between -F-Tyr-3 and His-5 residues within peptide substrates with concomitant and specific loss of fluorine. Our investigations suggest that a small intrinsic preference for coupling to fluorine is magnified by the binding of the peptide in a specific orientation that enforces the loss of fluorine during peptide crosslinking, likely a two-step reaction mechanism involving the non-enzyme catalysed reductive elimination of fluoride.

No Sex Differences in Perceptual Responses to High-Intensity Interval Training or Sprint Interval Training.

Coe, LN and Astorino, TA. No sex differences in perceptual responses to high-intensity interval training or sprint interval training. J Strength Cond Res 36(6): 1025-1032, 2024-High-intensity interval training (HIIT) elicits similar and, in some cases, superior benefits vs.

Reassignment of the Structure of a Tryptophan-Containing Cyclic Tripeptide Produced by the Biarylitide Crosslinking Cytochrome P450.

The structure of the sidechain crosslinked Tyr-Leu-Trp peptide produced by the biarylitide crosslinking cytochrome P450 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 in 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.