PERFORM Publications

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Title		Authors	PubMed ID
1	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
2	Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae.	Fossati E, Narcross L, Ekins A, Falgueyret JP, Martin VJ	25905794 BIOLOGY
3	Microbial Factories for the Production of Benzylisoquinoline Alkaloids.	Narcross L, Fossati E, Bourgeois L, Dueber JE, Martin VJJ	26775900 BIOLOGY
4	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
5	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
6	A Combinatorial Approach To Study Cytochrome P450 Enzymes for De Novo Production of Steviol Glucosides in Baker's Yeast.	Gold ND, Fossati E, Hansen CC, DiFalco M, Douchin V, Martin VJJ	30474973 CSFG

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
Publication:	PloS one
Keywords:
PMID:	25905794	Category:	PLoS One	Date Added:	2019-06-07
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]

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