An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides

Maxine Treisman; Laura Coe; Yongwei Zhao; Vishnu Mini Sasi; Jemma Gullick; Mathias H. Hansen; Aviva Ly; Victor Leichthammer; Caroline Hess; Daniel L. Machell; Ralf B. Schittenhelm; Joel Hooper; Colin J. Jackson; Julien Tailhades; James J. De Voss; Max J. Cryle

doi:10.1021/acs.orglett.3c04366

An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides

Maxine Treisman, Laura Coe, Yongwei Zhao, Vishnu Mini Sasi, Jemma Gullick, Mathias H. Hansen, Aviva Ly, Victor Leichthammer, Caroline Hess, Daniel L. Machell, Ralf B. Schittenhelm, Joel Hooper, Colin J. Jackson, Julien Tailhades, James J. De Voss, Max J. Cryle

Research output: Contribution to journal › Article › Research › peer-review

9 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1828-1833
Number of pages	6
Journal	Organic Letters
Volume	26
Issue number	9
DOIs	https://doi.org/10.1021/acs.orglett.3c04366
Publication status	Published - 28 Feb 2024

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10.1021/acs.orglett.3c04366Licence: CC BY

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Treisman, M., Coe, L., Zhao, Y., Sasi, V. M., Gullick, J., Hansen, M. H., Ly, A., Leichthammer, V., Hess, C., Machell, D. L., Schittenhelm, R. B., Hooper, J., Jackson, C. J., Tailhades, J., De Voss, J. J., & Cryle, M. J. (2024). An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides. Organic Letters, 26(9), 1828-1833. https://doi.org/10.1021/acs.orglett.3c04366

@article{46e6e6c21d5c41adb001b0b93a982f1d,

title = "An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides",

abstract = "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 P450Blt 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.",

author = "Maxine Treisman and Laura Coe and Yongwei Zhao and Sasi, {Vishnu Mini} and Jemma Gullick and Hansen, {Mathias H.} and Aviva Ly and Victor Leichthammer and Caroline Hess and Machell, {Daniel L.} and Schittenhelm, {Ralf B.} and Joel Hooper and Jackson, {Colin J.} and Julien Tailhades and {De Voss}, {James J.} and Cryle, {Max J.}",

note = "Funding Information: We thank Casey H. Londergan (Haverford) for helpful discussions and Monash University and EMBL Australia for support. This study used the BPA-enabled (Bioplatforms Australia)/NCRIS-enabled (National Collaborative Research Infrastructure Strategy) infrastructure located at the Monash Proteomics and Metabolomics Platform. This research was conducted by the Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science (CE200100012) and funded by the Australian Government. Publisher Copyright: {\textcopyright} 2024 The Authors. Published by American Chemical Society.",

year = "2024",

month = feb,

day = "28",

doi = "10.1021/acs.orglett.3c04366",

language = "English",

volume = "26",

pages = "1828--1833",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society",

number = "9",

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Treisman, M, Coe, L, Zhao, Y, Sasi, VM, Gullick, J, Hansen, MH, Ly, A, Leichthammer, V, Hess, C, Machell, DL, Schittenhelm, RB , Hooper, J, Jackson, CJ, Tailhades, J, De Voss, JJ & Cryle, MJ 2024, 'An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides', Organic Letters, vol. 26, no. 9, pp. 1828-1833. https://doi.org/10.1021/acs.orglett.3c04366

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T1 - An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides

AU - Treisman, Maxine

AU - Coe, Laura

AU - Zhao, Yongwei

AU - Sasi, Vishnu Mini

AU - Gullick, Jemma

AU - Hansen, Mathias H.

AU - Ly, Aviva

AU - Leichthammer, Victor

AU - Hess, Caroline

AU - Machell, Daniel L.

AU - Schittenhelm, Ralf B.

AU - Hooper, Joel

AU - Jackson, Colin J.

AU - Tailhades, Julien

AU - De Voss, James J.

AU - Cryle, Max J.

N1 - Funding Information: We thank Casey H. Londergan (Haverford) for helpful discussions and Monash University and EMBL Australia for support. This study used the BPA-enabled (Bioplatforms Australia)/NCRIS-enabled (National Collaborative Research Infrastructure Strategy) infrastructure located at the Monash Proteomics and Metabolomics Platform. This research was conducted by the Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science (CE200100012) and funded by the Australian Government. Publisher Copyright: © 2024 The Authors. Published by American Chemical Society.

PY - 2024/2/28

Y1 - 2024/2/28

N2 - 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 P450Blt 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.

AB - 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 P450Blt 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.

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JF - Organic Letters

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An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides

Abstract

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ARC Centre of Excellence for Innovations in Peptide and Protein Science

Monash Proteomics & Metabolomics Platform (MPMP)

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An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides

Abstract

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ARC Centre of Excellence for Innovations in Peptide and Protein Science

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Monash Proteomics & Metabolomics Platform (MPMP)

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