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An engineered combinatorial module of transcription factors boosts production of monoterpenoid indole alkaloids in Catharanthus roseus

Schweizer, Fabian ; Colinas, Maite ; Pollier, Jacob ; Van Moerkercke, Alex LU ; Vanden Bossche, Robin ; de Clercq, Rebecca and Goossens, Alain (2018) In Metabolic Engineering 48. p.150-162
Abstract

To fend off microbial pathogens and herbivores, plants have evolved a wide range of defense strategies such as physical barriers, or the production of anti-digestive proteins or bioactive specialized metabolites. Accumulation of the latter compounds is often regulated by transcriptional activation of the biosynthesis pathway genes by the phytohormone jasmonate-isoleucine. Here, we used our recently developed flower petal transformation method in the medicinal plant Catharanthus roseus to shed light on the complex regulatory mechanisms steering the jasmonate-modulated biosynthesis of monoterpenoid indole alkaloids (MIAs), to which the anti-cancer compounds vinblastine and vincristine belong. By combinatorial overexpression of the... (More)

To fend off microbial pathogens and herbivores, plants have evolved a wide range of defense strategies such as physical barriers, or the production of anti-digestive proteins or bioactive specialized metabolites. Accumulation of the latter compounds is often regulated by transcriptional activation of the biosynthesis pathway genes by the phytohormone jasmonate-isoleucine. Here, we used our recently developed flower petal transformation method in the medicinal plant Catharanthus roseus to shed light on the complex regulatory mechanisms steering the jasmonate-modulated biosynthesis of monoterpenoid indole alkaloids (MIAs), to which the anti-cancer compounds vinblastine and vincristine belong. By combinatorial overexpression of the transcriptional activators BIS1, ORCA3 and MYC2a, we provide an unprecedented insight into the modular transcriptional control of MIA biosynthesis. Furthermore, we show that the expression of an engineered de-repressed MYC2a triggers a tremendous reprogramming of the MIA pathway, finally leading to massively increased accumulation of at least 23 MIAs. The current study unveils an innovative approach for future metabolic engineering efforts for the production of valuable bioactive plant compounds in non-model plants.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Metabolic Engineering
volume
48
pages
13 pages
publisher
Elsevier
external identifiers
  • scopus:85048097641
  • pmid:29852273
ISSN
1096-7176
DOI
10.1016/j.ymben.2018.05.016
language
English
LU publication?
no
id
c4616b4a-1fba-4aeb-bd45-81ab43532ec0
date added to LUP
2018-12-19 11:44:42
date last changed
2024-04-15 19:30:10
@article{c4616b4a-1fba-4aeb-bd45-81ab43532ec0,
  abstract     = {{<p>To fend off microbial pathogens and herbivores, plants have evolved a wide range of defense strategies such as physical barriers, or the production of anti-digestive proteins or bioactive specialized metabolites. Accumulation of the latter compounds is often regulated by transcriptional activation of the biosynthesis pathway genes by the phytohormone jasmonate-isoleucine. Here, we used our recently developed flower petal transformation method in the medicinal plant Catharanthus roseus to shed light on the complex regulatory mechanisms steering the jasmonate-modulated biosynthesis of monoterpenoid indole alkaloids (MIAs), to which the anti-cancer compounds vinblastine and vincristine belong. By combinatorial overexpression of the transcriptional activators BIS1, ORCA3 and MYC2a, we provide an unprecedented insight into the modular transcriptional control of MIA biosynthesis. Furthermore, we show that the expression of an engineered de-repressed MYC2a triggers a tremendous reprogramming of the MIA pathway, finally leading to massively increased accumulation of at least 23 MIAs. The current study unveils an innovative approach for future metabolic engineering efforts for the production of valuable bioactive plant compounds in non-model plants.</p>}},
  author       = {{Schweizer, Fabian and Colinas, Maite and Pollier, Jacob and Van Moerkercke, Alex and Vanden Bossche, Robin and de Clercq, Rebecca and Goossens, Alain}},
  issn         = {{1096-7176}},
  language     = {{eng}},
  pages        = {{150--162}},
  publisher    = {{Elsevier}},
  series       = {{Metabolic Engineering}},
  title        = {{An engineered combinatorial module of transcription factors boosts production of monoterpenoid indole alkaloids in Catharanthus roseus}},
  url          = {{http://dx.doi.org/10.1016/j.ymben.2018.05.016}},
  doi          = {{10.1016/j.ymben.2018.05.016}},
  volume       = {{48}},
  year         = {{2018}},
}