Treisman Maxine, Coe Laura, Zhao Yongwei, Sasi Vishnu Mini, Gullick Jemma, Hansen Mathias H, Ly Aviva, Leichthammer Victor, Hess Caroline, Machell Daniel L, Schittenhelm Ralf B, Hooper Joel, Jackson Colin J, Tailhades Julien, De Voss James J, Cryle Max J
Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute, Monash University, EMBL Australia, Clayton, VIC 3800, Australia.
ARC Centre of Excellence for Innovations in Peptide and Protein Science, Clayton, VIC 3800, Australia.
Org Lett. 2024 Mar 8;26(9):1828-1833. doi: 10.1021/acs.orglett.3c04366. Epub 2024 Feb 28.
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 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.
细胞色素P450介导的核糖体编码肽(RiPPs)交联正在迅速发展,并在生物催化方面显示出巨大潜力。在此,我们证明了联芳肽交联酶P450的活性位点工程能够形成His-X-Tyr和Tyr-X-Tyr交联肽,从而展示了如何进一步利用此类P450来生产具有可控交联状态的交替环三肽。