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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
Author Correction: Building a global alliance of biofoundries.

Author(s): Hillson N, Caddick M, Cai Y, Carrasco JA, Chang MW, Curach NC, Bell DJ, Feuvre RL, Friedman DC, Fu X, Gold ND, Herrgård MJ, Holowko MB, John...

Nat Commun. 2019 Jul 11;10(1):3132 Authors: Hillson N, Caddick M, Cai Y, Carrasco JA, Chang MW, Curach NC, Bell DJ, Feuvre RL, Friedman DC, Fu X, Gold ND, Herrgård MJ, Holowko MB, Johnson JR,...

Article GUID: 31296848
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
A Highly Characterized Synthetic Landing Pad System for Precise Multicopy Gene Integration in Yeast.

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

ACS Synth Biol. 2018 Nov 16;7(11):2675-2685 Authors: Bourgeois L, Pyne ME, Martin VJJ

Article GUID: 30372609
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
Determinants of selection in yeast evolved by genome shuffling.

Author(s): Biot-Pelletier D, Pinel D, Larue K, Martin VJJ

Biotechnol Biofuels. 2018;11:282 Authors: Biot-Pelletier D, Pinel D, Larue K, Martin VJJ

Article GUID: 30356826
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
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
Building a global alliance of biofoundries.

Author(s): Hillson N, Caddick M, Cai Y, Carrasco JA, Chang MW, Curach NC, Bell DJ, Le Feuvre R, Friedman DC, Fu X, Gold ND, Herrgård MJ, Holowko MB, Jo...

Nat Commun. 2019 05 09;10(1):2040 Authors: Hillson N, Caddick M, Cai Y, Carrasco JA, Chang MW, Curach NC, Bell DJ, Le Feuvre R, Friedman DC, Fu X, Gold ND, Herrgård MJ, Holowko MB, Johnson JR...

Article GUID: 31068573
Title:A yeast platform for high-level synthesis of tetrahydroisoquinoline alkaloids.
Authors:Pyne ME,  Kevvai K,  Grewal PS,  Narcross L,  Choi B,  Bourgeois L,  Dueber JE,  Martin VJJ
Link:https://www.ncbi.nlm.nih.gov/pubmed/32620756?dopt=Abstract
DOI:10.1038/s41467-020-17172-x
Category:Nat Commun
PMID:32620756
Dept Affiliation: BIOLOGY
1 Department of Biology, Concordia University, Montréal, QC, Canada.
2 Centre for Applied Synthetic Biology, Concordia University, Montréal, QC, Canada.
3 Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.
4 Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
5 Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
6 Department of Biology, Concordia University, Montréal, QC, Canada. vincent.martin@concordia.ca.
7 Centre for Applied Synthetic Biology, Concordia University, Montréal, QC, Canada. vincent.martin@concordia.ca.

Description:

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

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

Abstract

The tetrahydroisoquinoline (THIQ) moiety is a privileged substructure of many bioactive natural products and semi-synthetic analogs. Plants manufacture more than 3,000 THIQ alkaloids, including the opioids morphine and codeine. While microbial species have been engineered to synthesize a few compounds from the benzylisoquinoline alkaloid (BIA) family of THIQs, low product titers impede industrial viability and limit access to the full chemical space. Here we report a yeast THIQ platform by increasing production of the central BIA intermediate (S)-reticuline to 4.6?g?L-1, a 57,000-fold improvement over our first-generation strain. We show that gains in BIA output coincide with the formation of several substituted THIQs derived from amino acid catabolism. We use these insights to repurpose the Ehrlich pathway and synthesize an array of THIQ structures. This work provides a blueprint for building diverse alkaloid scaffolds and enables the targeted overproduction of thousands of THIQ products, including natural and semi-synthetic opioids.

PMID: 32620756 [PubMed - as supplied by publisher]