biostudies-literatureTreisman MAustralian GovernmentAustralian Research Council1828-1833https://www.ebi.ac.uk/biostudies/studies/S-EPMC10929621biostudies-literatureUnknown26(9)Cytochrome-P450-mediated cross-linking of ribosomally encoded peptides (RiPPs) is rapidly expanding and displays great potential for biocatalysis. Here, we demonstrate that active site engineering of the biarylitide cross-linking enzyme P450_Blt enables the formation of His-X-Tyr and Tyr-X-Tyr cross-linked peptides, thus showing how such P450s can be further exploited to produce alternate cyclic tripeptides with controlled cross-linking states.Organic lettersAn Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides.PMC10929621CE200100012Coe LHess CMachell DLSasi VMHansen MHLy AGullick JLeichthammer VZhao YHooper JTreisman MCryle MJSchittenhelm RBJackson CJDe Voss JJTailhades JfalseAn Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides.Cytochrome-P450-mediated cross-linking of ribosomally encoded peptides (RiPPs) is rapidly expanding and displays great potential for biocatalysis. Here, we demonstrate that active site engineering of the biarylitide cross-linking enzyme P450_Blt enables the formation of His-X-Tyr and Tyr-X-Tyr cross-linked peptides, thus showing how such P450s can be further exploited to produce alternate cyclic tripeptides with controlled cross-linking states.2024-01-01T00:00:00Z2024 Mar2025-04-22T20:09:10.123Z2025-04-06T03:01:49.567ZS-EPMC109296213841782210.1021/acs.orglett.3c04366