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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:Reconstituting Plant Secondary Metabolism in Saccharomyces cerevisiae for Production of High-Value Benzylisoquinoline Alkaloids.
Authors:Pyne ME,  Narcross L,  Fossati E,  Bourgeois L,  Burton E,  Gold ND,  Martin VJ
Link:https://www.ncbi.nlm.nih.gov/pubmed/27417930?dopt=Abstract
DOI:10.1016/bs.mie.2016.02.011
Category:Methods Enzymol
PMID:27417930
Dept Affiliation: GENOMICS
1 Centre for Structural and Functional Genomics, Concordia University, Montréal, QC, Canada.
2 Centre for Structural and Functional Genomics, Concordia University, Montréal, QC, Canada. Electronic address: vincent.martin@concordia.ca.

Description:

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

Methods Enzymol. 2016;575:195-224

Authors: Pyne ME, Narcross L, Fossati E, Bourgeois L, Burton E, Gold ND, Martin VJ

Abstract

Benzylisoquinoline alkaloids (BIAs) constitute a diverse class of plant secondary metabolites that includes the opiate analgesics morphine and codeine. Collectively, BIAs exhibit a myriad of pharmacological activities, including antimicrobial, antitussive, antispasmodic, and anticancer properties. Despite 2500 known BIA products, only a small proportion are currently produced though traditional crop-based manufacturing, as complex stereochemistry renders chemical synthesis of BIAs largely unfeasible. The advent of synthetic biology and sophisticated microbial engineering coupled with recent advances in the elucidation of plant BIA metabolic networks has provided growing motivation for producing high-value BIAs in microbial hosts. Here, we provide a technical basis for reconstituting BIA biosynthetic pathways in the common yeast Saccharomyces cerevisiae. Methodologies outlined in this chapter include fundamental techniques for expressing and assaying BIA biosynthetic enzymes, bioprospecting large libraries of BIA enzyme variants, and reconstituting and optimizing complete BIA formation pathways in yeast. To expedite construction of superior BIA-producing yeast strains, we emphasize high-throughput techniques. Finally, we identify fundamental challenges impeding deployment of yeast-based BIA production platforms and briefly outline future prospects to overcome such barriers.

PMID: 27417930 [PubMed - indexed for MEDLINE]