Lana Vianey

Myxarylin: Total In Vitro Biosynthesis, Expansion of Substrate Scope, and Bioengineered Thioamidated Biarylitides Biarylitides are a new class of ribosomally synthesized and post-translationally modified peptides (RiPPs) featuring the smallest reported precursor peptide and cytochrome P450-mediated cross-links. Here, we report the complete in vitro reconstitution of the myxobacterial biarylitide, myxarylin. We demonstrate that cross-linking is the first step and acts as a gatekeeper for downstream processing. The cytochrome P450 enzyme P450BytO from the myxarylin biosynthetic gene cluster exhibits remarkable substrate tolerance, allowing biosynthesis of new-to-nature thioamidated biarylitides through an unprecedented modular precursor peptide engineering approach. Surprisingly, changes in the precursor peptide sequence resulted in a shift in the installation of the P450BytO-mediated modification from the expected C- to the N-terminus. Leader peptide removal follows cross-linking and is likely carried out by a prolyl oligopeptidase (POP), a member of the serine protease family. The last step of the pathway involves N-terminal methylation, which also prevents premature degradation of the pathway intermediates by the POP. The crystal structure of the methyltransferase in complex with SAH and myxarylin allowed us to rationalize its substrate selectivity and guide protein engineering to expand its substrate scope.

🔗 Full article here: pubs.acs.org/doi/full/10....

New paper out in JACS!

“Myxarylin: Total In Vitro Biosynthesis, Expansion of Substrate Scope, and Bioengineered Thioamidated Biarylitides”

DOI: 10.1021/jacs.5c17257

We reconstitute a minimal biarylitide RiPP pathway and reveal the plasticity of P450 BytO.

#NaturalProducts #Biosynthesis #RiPPs

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I am really happy that I was able to present my first PhD results and I am grateful to the jury for this prize 🦠🧬