PERFORM Publications

Keyword search (4,163 papers available)

Title		Authors	PubMed ID
1	Pathway elucidation and microbial synthesis of proaporphine and bis-benzylisoquinoline alkaloids from sacred lotus (Nelumbo nucifera)	Pyne ME; Gold ND; Martin VJJ;	37004909 BIOLOGY
2	Author Correction: Building a global alliance of biofoundries.	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, Johnson RA, Keasling JD, Kitney RI, Kondo A, Liu C, Martin VJJ, Menolascina F, Ogino C, Patron NJ, Pavan M, Poh CL, Pretorius IS, Rosser SJ, Scrutton NS, Storch M, Tekotte H, Travnik E, Vickers CE, Yew WS, Yuan Y, Zhao H, Freemont PS	31296848 CHEMBIOCHEM
3	Global view of the Clostridium thermocellum cellulosome revealed by quantitative proteomic analysis.	Gold ND, Martin VJ	17644599 BIOLOGY
4	Expression of a library of fungal β-glucosidases in Saccharomyces cerevisiae for the development of a biomass fermenting strain.	Wilde C, Gold ND, Bawa N, Tambor JH, Mougharbel L, Storms R, Martin VJ	22218767 CSFG
5	Metabolic engineering of a tyrosine-overproducing yeast platform using targeted metabolomics.	Gold ND, Gowen CM, Lussier FX, Cautha SC, Mahadevan R, Martin VJ	26016674 CSFG
6	Engineering of a Nepetalactol-Producing Platform Strain of Saccharomyces cerevisiae for the Production of Plant Seco-Iridoids.	Campbell A, Bauchart P, Gold ND, Zhu Y, De Luca V, Martin VJ	26981892 CSFG
7	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
8	Pyrenoid functions revealed by proteomics in Chlamydomonas reinhardtii	Zhan Y; Marchand CH; Maes A; Mauries A; Sun Y; Dhaliwal JS; Uniacke J; Arragain S; Jiang H; Gold ND; Martin VJJ; Lemaire SD; Zerges W;	29481573 CSFG
9	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
10	Building a global alliance of biofoundries.	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, Johnson RA, Keasling JD, Kitney RI, Kondo A, Liu C, Martin VJJ, Menolascina F, Ogino C, Patron NJ, Pavan M, Poh CL, Pretorius IS, Rosser SJ, Scrutton NS, Storch M, Tekotte H, Travnik E, Vickers CE, Yew WS, Yuan Y, Zhao H, Freemont PS	31068573 CHEMBIOCHEM

Title:	Metabolic engineering of a tyrosine-overproducing yeast platform using targeted metabolomics.
Authors:	Gold ND, Gowen CM, Lussier FX, Cautha SC, Mahadevan R, Martin VJ
Link:	https://www.ncbi.nlm.nih.gov/pubmed/26016674?dopt=Abstract
DOI:	10.1186/s12934-015-0252-2
Publication:	Microbial cell factories
Keywords:
PMID:	26016674	Category:	Microb Cell Fact	Date Added:	2019-06-07
Dept Affiliation:	CSFG 1 Department of Biology and Centre for Structural and Functional Genomics, Concordia University, 7141 Sherbrooke West, Montreal, QC, H4B 1R6, Canada. nicholas.gold@concordia.ca. 2 Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada. chris.gowen@utoronto.ca. 3 Department of Biology and Centre for Structural and Functional Genomics, Concordia University, 7141 Sherbrooke West, Montreal, QC, H4B 1R6, Canada. fx.lussier@concordia.ca. 4 Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada. sarat.cautha@utoronto.ca. 5 Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada. krishna.mahadevan@utoronto.ca. 6 Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada. krishna.mahadevan@utoronto.ca. 7 Department of Biology and Centre for Structural and Functional Genomics, Concordia University, 7141 Sherbrooke West, Montreal, QC, H4B 1R6, Canada. vincent.martin@concordia.ca.

Description:

Metabolic engineering of a tyrosine-overproducing yeast platform using targeted metabolomics.

Microb Cell Fact. 2015 May 28;14:73

Authors: Gold ND, Gowen CM, Lussier FX, Cautha SC, Mahadevan R, Martin VJ

Abstract

BACKGROUND: L-tyrosine is a common precursor for a wide range of valuable secondary metabolites, including benzylisoquinoline alkaloids (BIAs) and many polyketides. An industrially tractable yeast strain optimized for production of L-tyrosine could serve as a platform for the development of BIA and polyketide cell factories. This study applied a targeted metabolomics approach to evaluate metabolic engineering strategies to increase the availability of intracellular L-tyrosine in the yeast Saccharomyces cerevisiae CEN.PK. Our engineering strategies combined localized pathway engineering with global engineering of central metabolism, facilitated by genome-scale steady-state modelling.

RESULTS: Addition of a tyrosine feedback resistant version of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase Aro4 from S. cerevisiae was combined with overexpression of either a tyrosine feedback resistant yeast chorismate mutase Aro7, the native pentafunctional arom protein Aro1, native prephenate dehydrogenase Tyr1 or cyclohexadienyl dehydrogenase TyrC from Zymomonas mobilis. Loss of aromatic carbon was limited by eliminating phenylpyruvate decarboxylase Aro10. The TAL gene from Rhodobacter sphaeroides was used to produce coumarate as a simple test case of a heterologous by-product of tyrosine. Additionally, multiple strategies for engineering global metabolism to promote tyrosine production were evaluated using metabolic modelling. The T21E mutant of pyruvate kinase Cdc19 was hypothesized to slow the conversion of phosphoenolpyruvate to pyruvate and accumulate the former as precursor to the shikimate pathway. The ZWF1 gene coding for glucose-6-phosphate dehydrogenase was deleted to create an NADPH deficiency designed to force the cell to couple its growth to tyrosine production via overexpressed NADP(+)-dependent prephenate dehydrogenase Tyr1. Our engineered Zwf1(-) strain expressing TYRC ARO4(FBR) and grown in the presence of methionine achieved an intracellular L-tyrosine accumulation up to 520 µmol/g DCW or 192 mM in the cytosol, but sustained flux through this pathway was found to depend on the complete elimination of feedback inhibition and degradation pathways.

CONCLUSIONS: Our targeted metabolomics approach confirmed a likely regulatory site at DAHP synthase and identified another possible cofactor limitation at prephenate dehydrogenase. Additionally, the genome-scale metabolic model identified design strategies that have the potential to improve availability of erythrose 4-phosphate for DAHP synthase and cofactor availability for prephenate dehydrogenase. We evaluated these strategies and provide recommendations for further improvement of aromatic amino acid biosynthesis in S. cerevisiae.

PMID: 26016674 [PubMed - indexed for MEDLINE]

BookR: School of Health Core Facilities Booking

"Gold ND" Authored Publications:

Search Publications

No results