Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide

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Standard

Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide. / Hansen, Nikolaj Lervad; Kjaerulff, Louise; Heck, Quinn Kalby; Forman, Victor; Stærk, Dan; Møller, Birger Lindberg; Andersen-Ranberg, Johan.

I: Nature Communications, Bind 13, 5011, 2022.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Hansen, NL, Kjaerulff, L, Heck, QK, Forman, V, Stærk, D, Møller, BL & Andersen-Ranberg, J 2022, 'Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide', Nature Communications, bind 13, 5011. https://doi.org/10.1038/s41467-022-32667-5

APA

Hansen, N. L., Kjaerulff, L., Heck, Q. K., Forman, V., Stærk, D., Møller, B. L., & Andersen-Ranberg, J. (2022). Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide. Nature Communications, 13, [5011]. https://doi.org/10.1038/s41467-022-32667-5

Vancouver

Hansen NL, Kjaerulff L, Heck QK, Forman V, Stærk D, Møller BL o.a. Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide. Nature Communications. 2022;13. 5011. https://doi.org/10.1038/s41467-022-32667-5

Author

Hansen, Nikolaj Lervad ; Kjaerulff, Louise ; Heck, Quinn Kalby ; Forman, Victor ; Stærk, Dan ; Møller, Birger Lindberg ; Andersen-Ranberg, Johan. / Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide. I: Nature Communications. 2022 ; Bind 13.

Bibtex

@article{55b29b7d0cba48c785279a4f4ed5f7de,
title = "Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide",
abstract = "The diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment and as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) from the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosynthesis of the abeo-abietane core structure present in diterpenoid triepoxides and in several other plant diterpenoids. In combination with two CYPs of the CYP82D subfamily, four CYPs from T. wilfordii are shown to constitute the minimal set of biosynthetic genes that enables triptonide biosynthesis using Nicotiana benthamiana and Saccharomyces cerevisiae as heterologous hosts. In addition, co-expression of a specific T. wilfordii cytochrome b5 (Twcytb5-A) increases triptonide output more than 9-fold in S. cerevisiae and affords isolation and structure elucidation by NMR spectroscopic analyses of 18 diterpenoids, providing insights into the biosynthesis of diterpenoid triepoxides. Our findings pave the way for diterpenoid triepoxide production via fermentation.",
author = "Hansen, {Nikolaj Lervad} and Louise Kjaerulff and Heck, {Quinn Kalby} and Victor Forman and Dan St{\ae}rk and M{\o}ller, {Birger Lindberg} and Johan Andersen-Ranberg",
year = "2022",
doi = "10.1038/s41467-022-32667-5",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide

AU - Hansen, Nikolaj Lervad

AU - Kjaerulff, Louise

AU - Heck, Quinn Kalby

AU - Forman, Victor

AU - Stærk, Dan

AU - Møller, Birger Lindberg

AU - Andersen-Ranberg, Johan

PY - 2022

Y1 - 2022

N2 - The diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment and as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) from the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosynthesis of the abeo-abietane core structure present in diterpenoid triepoxides and in several other plant diterpenoids. In combination with two CYPs of the CYP82D subfamily, four CYPs from T. wilfordii are shown to constitute the minimal set of biosynthetic genes that enables triptonide biosynthesis using Nicotiana benthamiana and Saccharomyces cerevisiae as heterologous hosts. In addition, co-expression of a specific T. wilfordii cytochrome b5 (Twcytb5-A) increases triptonide output more than 9-fold in S. cerevisiae and affords isolation and structure elucidation by NMR spectroscopic analyses of 18 diterpenoids, providing insights into the biosynthesis of diterpenoid triepoxides. Our findings pave the way for diterpenoid triepoxide production via fermentation.

AB - The diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment and as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) from the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosynthesis of the abeo-abietane core structure present in diterpenoid triepoxides and in several other plant diterpenoids. In combination with two CYPs of the CYP82D subfamily, four CYPs from T. wilfordii are shown to constitute the minimal set of biosynthetic genes that enables triptonide biosynthesis using Nicotiana benthamiana and Saccharomyces cerevisiae as heterologous hosts. In addition, co-expression of a specific T. wilfordii cytochrome b5 (Twcytb5-A) increases triptonide output more than 9-fold in S. cerevisiae and affords isolation and structure elucidation by NMR spectroscopic analyses of 18 diterpenoids, providing insights into the biosynthesis of diterpenoid triepoxides. Our findings pave the way for diterpenoid triepoxide production via fermentation.

U2 - 10.1038/s41467-022-32667-5

DO - 10.1038/s41467-022-32667-5

M3 - Journal article

C2 - 36008399

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 5011

ER -

ID: 317169644