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Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae.

Author(s): Fossati E, Ekins A, Narcross L, Zhu Y, Falgueyret JP, Beaudoin GA, Facchini PJ, Martin VJ

Nat Commun. 2014;5:3283 Authors: Fossati E, Ekins A, Narcross L, Zhu Y, Falgueyret JP, Beaudoin GA, Facchini PJ, Martin VJ

Article GUID: 24513861
Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae.

Author(s): Fossati E, Narcross L, Ekins A, Falgueyret JP, Martin VJ

PLoS One. 2015;10(4):e0124459 Authors: Fossati E, Narcross L, Ekins A, Falgueyret JP, Martin VJ

Article GUID: 25905794
Microbial Factories for the Production of Benzylisoquinoline Alkaloids.

Author(s): Narcross L, Fossati E, Bourgeois L, Dueber JE, Martin VJJ

Trends Biotechnol. 2016 Mar;34(3):228-241 Authors: Narcross L, Fossati E, Bourgeois L, Dueber JE, Martin VJJ

Article GUID: 26775900
Reconstituting Plant Secondary Metabolism in Saccharomyces cerevisiae for Production of High-Value Benzylisoquinoline Alkaloids.

Author(s): Pyne ME, Narcross L, Fossati E, Bourgeois L, Burton E, Gold ND, Martin VJ

Methods Enzymol. 2016;575:195-224 Authors: Pyne ME, Narcross L, Fossati E, Bourgeois L, Burton E, Gold ND, Martin VJ

Article GUID: 27417930
Mining Enzyme Diversity of Transcriptome Libraries through DNA Synthesis for Benzylisoquinoline Alkaloid Pathway Optimization in Yeast.

Author(s): Narcross L, Bourgeois L, Fossati E, Burton E, Martin VJ

ACS Synth Biol. 2016 12 16;5(12):1505-1518 Authors: Narcross L, Bourgeois L, Fossati E, Burton E, Martin VJ

Article GUID: 27442619
A Combinatorial Approach To Study Cytochrome P450 Enzymes for De Novo Production of Steviol Glucosides in Baker's Yeast.

Author(s): Gold ND, Fossati E, Hansen CC, DiFalco M, Douchin V, Martin VJJ

ACS Synth Biol. 2018 Dec 21;7(12):2918-2929 Authors: Gold ND, Fossati E, Hansen CC, DiFalco M, Douchin V, Martin VJJ

Article GUID: 30474973
Title:Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae.
Authors:Fossati E,  Ekins A,  Narcross L,  Zhu Y,  Falgueyret JP,  Beaudoin GA,  Facchini PJ,  Martin VJ
Link:https://www.ncbi.nlm.nih.gov/pubmed/24513861?dopt=Abstract
DOI:10.1038/ncomms4283
Category:Nat Commun
PMID:24513861
Dept Affiliation: BIOLOGY
1 1] Department of Biology, Concordia University, Montréal, Québec, Canada H4B 1R6 [2] Centre for Structural and Functional Genomics, Concordia University, Montréal, Québec, Canada H4B 1R6 [3].
2 1] Department of Biology, Concordia University, Montréal, Québec, Canada H4B 1R6 [2] Centre for Structural and Functional Genomics, Concordia University, Montréal, Québec, Canada H4B 1R6.
3 Centre for Structural and Functional Genomics, Concordia University, Montréal, Québec, Canada H4B 1R6.
4 Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada T2N 1N4.

Description:

Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae.

Nat Commun. 2014;5:3283

Authors: Fossati E, Ekins A, Narcross L, Zhu Y, Falgueyret JP, Beaudoin GA, Facchini PJ, Martin VJ

Abstract

Benzylisoquinoline alkaloids (BIAs) represent a large class of plant secondary metabolites, including pharmaceuticals such as morphine, codeine and their derivatives. Large-scale production of BIA-based pharmaceuticals is limited to extraction and derivatization of alkaloids that accumulate in planta. Synthesis of BIAs in microbial hosts could bypass such limitations and transform both industrial production of BIAs with recognized value and research into uncharacterized BIAs. Here we reconstitute a 10-gene plant pathway in Saccharomyces cerevisiae that allows for the production of dihydrosanguinarine and its oxidized derivative sanguinarine from (R,S)-norlaudanosoline. Synthesis of dihydrosanguinarine also yields the side-products N-methylscoulerine and N-methylcheilanthifoline, the latter of which has not been detected in plants. This work represents the longest reconstituted alkaloid pathway ever assembled in yeast and demonstrates the feasibility of the production of high-value alkaloids in microbial systems.

PMID: 24513861 [PubMed - indexed for MEDLINE]