Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast

Research output: Contribution to journal › Journal article › Research › peer-review

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Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast. / Bradley, Samuel A.; Lehka, Beata J.; Hansson, Frederik G.; Adhikari, Khem B.; Rago, Daniela; Rubaszka, Paulina; Haidar, Ahmad K.; Chen, Ling; Hansen, Lea G.; Gudich, Olga; Giannakou, Konstantina; Lengger, Bettina; Gill, Ryan T.; Nakamura, Yoko; de Bernonville, Thomas Dugé; Koudounas, Konstantinos; Romero-Suarez, David; Ding, Ling; Qiao, Yijun; Frimurer, Thomas M.; Petersen, Anja A.; Besseau, Sébastien; Kumar, Sandeep; Gautron, Nicolas; Melin, Celine; Marc, Jillian; Jeanneau, Remi; O’Connor, Sarah E.; Courdavault, Vincent; Keasling, Jay D.; Zhang, Jie; Jensen, Michael K.

In: Nature Chemical Biology, Vol. 19, No. 12, 2023, p. 1551-1560.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bradley, SA, Lehka, BJ, Hansson, FG, Adhikari, KB, Rago, D, Rubaszka, P, Haidar, AK, Chen, L, Hansen, LG, Gudich, O, Giannakou, K, Lengger, B, Gill, RT, Nakamura, Y, de Bernonville, TD, Koudounas, K, Romero-Suarez, D, Ding, L, Qiao, Y, Frimurer, TM, Petersen, AA, Besseau, S, Kumar, S, Gautron, N, Melin, C, Marc, J, Jeanneau, R, O’Connor, SE, Courdavault, V, Keasling, JD, Zhang, J & Jensen, MK 2023, 'Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast', Nature Chemical Biology, vol. 19, no. 12, pp. 1551-1560. https://doi.org/10.1038/s41589-023-01430-2

APA

Bradley, S. A., Lehka, B. J., Hansson, F. G., Adhikari, K. B., Rago, D., Rubaszka, P., Haidar, A. K., Chen, L., Hansen, L. G., Gudich, O., Giannakou, K., Lengger, B., Gill, R. T., Nakamura, Y., de Bernonville, T. D., Koudounas, K., Romero-Suarez, D., Ding, L., Qiao, Y., ... Jensen, M. K. (2023). Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast. Nature Chemical Biology, 19(12), 1551-1560. https://doi.org/10.1038/s41589-023-01430-2

Vancouver

Bradley SA, Lehka BJ, Hansson FG, Adhikari KB, Rago D, Rubaszka P et al. Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast. Nature Chemical Biology. 2023;19(12):1551-1560. https://doi.org/10.1038/s41589-023-01430-2

Author

Bradley, Samuel A. ; Lehka, Beata J. ; Hansson, Frederik G. ; Adhikari, Khem B. ; Rago, Daniela ; Rubaszka, Paulina ; Haidar, Ahmad K. ; Chen, Ling ; Hansen, Lea G. ; Gudich, Olga ; Giannakou, Konstantina ; Lengger, Bettina ; Gill, Ryan T. ; Nakamura, Yoko ; de Bernonville, Thomas Dugé ; Koudounas, Konstantinos ; Romero-Suarez, David ; Ding, Ling ; Qiao, Yijun ; Frimurer, Thomas M. ; Petersen, Anja A. ; Besseau, Sébastien ; Kumar, Sandeep ; Gautron, Nicolas ; Melin, Celine ; Marc, Jillian ; Jeanneau, Remi ; O’Connor, Sarah E. ; Courdavault, Vincent ; Keasling, Jay D. ; Zhang, Jie ; Jensen, Michael K. / Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast. In: Nature Chemical Biology. 2023 ; Vol. 19, No. 12. pp. 1551-1560.

Bibtex

@article{eabc9eb1511e40658058b9f8c39815e2,

title = "Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast",

abstract = "Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker{\textquoteright}s yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential.",

author = "Bradley, {Samuel A.} and Lehka, {Beata J.} and Hansson, {Frederik G.} and Adhikari, {Khem B.} and Daniela Rago and Paulina Rubaszka and Haidar, {Ahmad K.} and Ling Chen and Hansen, {Lea G.} and Olga Gudich and Konstantina Giannakou and Bettina Lengger and Gill, {Ryan T.} and Yoko Nakamura and {de Bernonville}, {Thomas Dug{\'e}} and Konstantinos Koudounas and David Romero-Suarez and Ling Ding and Yijun Qiao and Frimurer, {Thomas M.} and Petersen, {Anja A.} and S{\'e}bastien Besseau and Sandeep Kumar and Nicolas Gautron and Celine Melin and Jillian Marc and Remi Jeanneau and O{\textquoteright}Connor, {Sarah E.} and Vincent Courdavault and Keasling, {Jay D.} and Jie Zhang and Jensen, {Michael K.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

doi = "10.1038/s41589-023-01430-2",

language = "English",

volume = "19",

pages = "1551--1560",

journal = "Nature Chemical Biology",

issn = "1552-4450",

publisher = "nature publishing group",

number = "12",

}

RIS

TY - JOUR

T1 - Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast

AU - Bradley, Samuel A.

AU - Lehka, Beata J.

AU - Hansson, Frederik G.

AU - Adhikari, Khem B.

AU - Rago, Daniela

AU - Rubaszka, Paulina

AU - Haidar, Ahmad K.

AU - Chen, Ling

AU - Hansen, Lea G.

AU - Gudich, Olga

AU - Giannakou, Konstantina

AU - Lengger, Bettina

AU - Gill, Ryan T.

AU - Nakamura, Yoko

AU - de Bernonville, Thomas Dugé

AU - Koudounas, Konstantinos

AU - Romero-Suarez, David

AU - Ding, Ling

AU - Qiao, Yijun

AU - Frimurer, Thomas M.

AU - Petersen, Anja A.

AU - Besseau, Sébastien

AU - Kumar, Sandeep

AU - Gautron, Nicolas

AU - Melin, Celine

AU - Marc, Jillian

AU - Jeanneau, Remi

AU - O’Connor, Sarah E.

AU - Courdavault, Vincent

AU - Keasling, Jay D.

AU - Zhang, Jie

AU - Jensen, Michael K.

PY - 2023

Y1 - 2023

N2 - Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker’s yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential.

AB - Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker’s yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential.

U2 - 10.1038/s41589-023-01430-2

DO - 10.1038/s41589-023-01430-2

M3 - Journal article

C2 - 37932529

AN - SCOPUS:85175793398

VL - 19

SP - 1551

EP - 1560

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4450

IS - 12

ER -

ID: 374932139