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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 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
Title:An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose.
Authors:DeLoache WC,  Russ ZN,  Narcross L,  Gonzales AM,  Martin VJ,  Dueber JE
Link:https://www.ncbi.nlm.nih.gov/pubmed/25984720?dopt=Abstract
DOI:10.1038/nchembio.1816
Category:Nat Chem Biol
PMID:25984720
Dept Affiliation: BIOLOGY
1 Department of Bioengineering, University of California, Berkeley, Berkeley, California, USA.
2 1] Department of Biology, Concordia University, Montréal, Québec, Canada. [2] Centre for Structural and Functional Genomics, Concordia University, Montréal, Québec, Canada.

Description:

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

Nat Chem Biol. 2015 Jul;11(7):465-71

Authors: DeLoache WC, Russ ZN, Narcross L, Gonzales AM, Martin VJ, Dueber JE

Abstract

Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant-specialized metabolites that include the pharmaceuticals codeine and morphine and their derivatives. Microbial synthesis of BIAs holds promise as an alternative to traditional crop-based manufacturing. Here we demonstrate the production of the key BIA intermediate (S)-reticuline from glucose in Saccharomyces cerevisiae. To aid in this effort, we developed an enzyme-coupled biosensor for the upstream intermediate L-3,4-dihydroxyphenylalanine (L-DOPA). Using this sensor, we identified an active tyrosine hydroxylase and improved its L-DOPA yields by 2.8-fold via PCR mutagenesis. Coexpression of DOPA decarboxylase enabled what is to our knowledge the first demonstration of dopamine production from glucose in yeast, with a 7.4-fold improvement in titer obtained for our best mutant enzyme. We extended this pathway to fully reconstitute the seven-enzyme pathway from L-tyrosine to (S)-reticuline. Future work to improve titers and connect these steps with downstream pathway branches, already demonstrated in S. cerevisiae, will enable low-cost production of many high-value BIAs.

PMID: 25984720 [PubMed - indexed for MEDLINE]