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A yeast platform for high-level synthesis of tetrahydroisoquinoline alkaloids.

Author(s): Pyne ME, Kevvai K, Grewal PS, Narcross L, Choi B, Bourgeois L, Dueber JE, Martin VJJ

Nat Commun. 2020 Jul 03;11(1):3337 Authors: Pyne ME, Kevvai K, Grewal PS, Narcross L, Choi B, Bourgeois L, Dueber JE, Martin VJJ

Article GUID: 32620756
An Engineered Aro1 Protein Degradation Approach for Increased cis,cis-Muconic Acid Biosynthesis in Saccharomyces cerevisiae.

Author(s): Pyne ME, Narcross L, Melgar M, Kevvai K, Mookerjee S, Leite GB, Martin VJJ

Appl Environ Microbiol. 2018 Sep 01;84(17): Authors: Pyne ME, Narcross L, Melgar M, Kevvai K, Mookerjee S, Leite GB, Martin VJJ

Article GUID: 29934332
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
An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose.

Author(s): DeLoache WC, Russ ZN, Narcross L, Gonzales AM, Martin VJ, Dueber JE

Nat Chem Biol. 2015 Jul;11(7):465-71 Authors: DeLoache WC, Russ ZN, Narcross L, Gonzales AM, Martin VJ, Dueber JE

Article GUID: 25984720
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
Engineering Plant Secondary Metabolism in Microbial Systems.

Author(s): Pyne ME, Narcross L, Martin VJJ

Plant Physiol. 2019 03;179(3):844-861 Authors: Pyne ME, Narcross L, Martin VJJ PMID: 30643013 [PubMed - indexed for MEDLINE]

Article GUID: 30643013
Title:Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae.
Authors:Fossati E,  Narcross L,  Ekins A,  Falgueyret JP,  Martin VJ
Link:https://www.ncbi.nlm.nih.gov/pubmed/25905794?dopt=Abstract
DOI:10.1371/journal.pone.0124459
Category:PLoS One
PMID:25905794
Dept Affiliation: BIOLOGY
1 Department of Biology, Concordia University, Montréal, Québec, Canada; Centre for Structural and Functional Genomics, Concordia University, Montréal, Québec, Canada.
2 Centre for Structural and Functional Genomics, Concordia University, Montréal, Québec, Canada.

Description:

Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae.

PLoS One. 2015;10(4):e0124459

Authors: Fossati E, Narcross L, Ekins A, Falgueyret JP, Martin VJ

Abstract

Morphinan alkaloids are the most powerful narcotic analgesics currently used to treat moderate to severe and chronic pain. The feasibility of morphinan synthesis in recombinant Saccharomyces cerevisiae starting from the precursor (R,S)-norlaudanosoline was investigated. Chiral analysis of the reticuline produced by the expression of opium poppy methyltransferases showed strict enantioselectivity for (S)-reticuline starting from (R,S)-norlaudanosoline. In addition, the P. somniferum enzymes salutaridine synthase (PsSAS), salutaridine reductase (PsSAR) and salutaridinol acetyltransferase (PsSAT) were functionally co-expressed in S. cerevisiae and optimization of the pH conditions allowed for productive spontaneous rearrangement of salutaridinol-7-O-acetate and synthesis of thebaine from (R)-reticuline. Finally, we reconstituted a 7-gene pathway for the production of codeine and morphine from (R)-reticuline. Yeast cell feeding assays using (R)-reticuline, salutaridine or codeine as substrates showed that all enzymes were functionally co-expressed in yeast and that activity of salutaridine reductase and codeine-O-demethylase likely limit flux to morphine synthesis. The results of this study describe a significant advance for the synthesis of morphinans in S. cerevisiae and pave the way for their complete synthesis in recombinant microbes.

PMID: 25905794 [PubMed - indexed for MEDLINE]