Keyword search (4,163 papers available)

"Narcross L" Authored Publications:

Title Authors PubMed ID
1 Benzylisoquinoline Alkaloid Production in Yeast via Norlaudanosoline Improves Titer, Selectivity, and Yield Narcross L; Pyne ME; Kevvai K; Siu KH; Dueber JE; Martin VJJ; 41779670
BIOLOGY
2 Sequencing of a Dairy Isolate Unlocks em Kluyveromyces marxianus /em as a Host for Lactose Valorization Thornbury M; Knoops A; Summerby-Murray I; Dhaliwal J; Johnson S; Utomo JC; Joshi J; Narcross L; Remondetto G; Pouliot M; Whiteway M; Martin VJJ; 40629255
BIOLOGY
3 Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid Pyne ME; Bagley JA; Narcross L; Kevvai K; Exley K; Davies M; Wang Q; Whiteway M; Martin VJJ; 37652930
BIOLOGY
4 A yeast platform for high-level synthesis of tetrahydroisoquinoline alkaloids. Pyne ME, Kevvai K, Grewal PS, Narcross L, Choi B, Bourgeois L, Dueber JE, Martin VJJ 32620756
BIOLOGY
5 An Engineered Aro1 Protein Degradation Approach for Increased cis,cis-Muconic Acid Biosynthesis in Saccharomyces cerevisiae. Pyne ME, Narcross L, Melgar M, Kevvai K, Mookerjee S, Leite GB, Martin VJJ 29934332
BIOLOGY
6 Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae. Fossati E, Ekins A, Narcross L, Zhu Y, Falgueyret JP, Beaudoin GA, Facchini PJ, Martin VJ 24513861
BIOLOGY
7 Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae. Fossati E, Narcross L, Ekins A, Falgueyret JP, Martin VJ 25905794
BIOLOGY
8 An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose. DeLoache WC, Russ ZN, Narcross L, Gonzales AM, Martin VJ, Dueber JE 25984720
BIOLOGY
9 Microbial Factories for the Production of Benzylisoquinoline Alkaloids. Narcross L, Fossati E, Bourgeois L, Dueber JE, Martin VJJ 26775900
BIOLOGY
10 Reconstituting Plant Secondary Metabolism in Saccharomyces cerevisiae for Production of High-Value Benzylisoquinoline Alkaloids. Pyne ME, Narcross L, Fossati E, Bourgeois L, Burton E, Gold ND, Martin VJ 27417930
CSFG
11 Mining Enzyme Diversity of Transcriptome Libraries through DNA Synthesis for Benzylisoquinoline Alkaloid Pathway Optimization in Yeast. Narcross L, Bourgeois L, Fossati E, Burton E, Martin VJ 27442619
BIOLOGY
12 Engineering Plant Secondary Metabolism in Microbial Systems. Pyne ME, Narcross L, Martin VJJ 30643013
CSFG

 

Title:Benzylisoquinoline Alkaloid Production in Yeast via Norlaudanosoline Improves Titer, Selectivity, and Yield
Authors:Narcross LPyne MEKevvai KSiu KHDueber JEMartin VJJ
Link:https://pubmed.ncbi.nlm.nih.gov/41779670/
DOI:10.1021/acssynbio.5c00897
Publication:ACS synthetic biology
Keywords:Saccharomyces cerevisiaebenzylisoquinoline alkaloidsmetabolic engineeringreticulinesynthetic biologyyeast
PMID:41779670 Category: Date Added:2026-03-04
Dept Affiliation: BIOLOGY
1 Department of Biology, Concordia University, Montréal, Québec H4B 1R6, Canada.
2 Centre for Applied Synthetic Biology, Concordia University, Montréal, Québec H4B 1R6, Canada.
3 Department of Bioengineering, University of California, Berkeley, Berkeley, California 94720, United States.
4 Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.

Description:

The benzylisoquinoline alkaloid (BIA) family of tetrahydroisoquinolines (THIQs) comprises >2,500 members, including the pharmaceuticals morphine, codeine, and papaverine, as well as the antibiotics sanguinarine and chelerythrine. Agricultural cultivation can supply the demand for the BIAs that accumulate in plants, but broader access to the BIA family would facilitate additional research and commercialization. Microbial synthesis presents an attractive option due to cheap feedstock, genetic tractability, and ease of scale-up. Previously, we reported titers of the branch-point BIA (S)-reticuline of 4.6 g/L in yeast, which was achieved through leveraging the Ehrlich pathway 2-oxoacid decarboxylase Aro10 to generate the intermediate 4-hydroxyphenylacetaldehyde (4-HPAA). Here, we establish a superior route to (S)-reticuline by switching the pathway intermediate from 4-HPAA to 3,4-dihydroxyphenylacetaldehyde (3,4-dHPAA) using monoamine oxidase A (MAO). The resulting (S)-norlaudanosoline route to (S)-reticuline synthesis is more selective, resolving prior issues with off-pathway THIQs synthesized due to cascading enzyme promiscuity, and more efficient, enabling titers of 4.8 g/L (S)-reticuline while improving yields by over 40%, from 17 to 24 mg/g sucrose in fed-batch fermentations. Finally, we extend de novo (S)-reticuline synthesis to dihydrosanguinarine, achieving 635 mg/L dihydrosanguinarine and sanguinarine in fed-batch fermentation, the highest reported titer of these BIAs by a factor of 40.





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