Keyword search (4,163 papers available)

"Knoops A" Authored Publications:

Title Authors PubMed ID
1 Tri-Functional CRISPR Screen Reveals Overexpression of em QDR2 /em and em QDR3 /em Transporters Increase Fumaric Acid Production in em Kluyveromyces marxianus /em Thornbury M; Omran RP; Kumar L; Knoops A; Abushahin R; Whiteway M; Martin VJJ; 41277095
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

 

Title:Tri-Functional CRISPR Screen Reveals Overexpression of em QDR2 /em and em QDR3 /em Transporters Increase Fumaric Acid Production in em Kluyveromyces marxianus /em
Authors:Thornbury MOmran RPKumar LKnoops AAbushahin RWhiteway MMartin VJJ
Link:https://pubmed.ncbi.nlm.nih.gov/41277095/
DOI:10.1021/acssynbio.5c00689
Publication:ACS synthetic biology
Keywords:CRISPRacid tolerancefermentationfumaric acidgenome-wide engineeringkluyveromyces
PMID:41277095 Category: Date Added:2025-11-24
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 Concordia Bioprocessing, Montréal, Québec H4B 1R6, Canada.
4 Concordia Genome Foundry, Montréal, Québec H4B 1R6, Canada.
5 Centre for Structural and Functional Genomics, Concordia University, Montréal, Québec H4B 1R6, Canada.

Description:

Organic acids such as fumaric acid are widely used in the food and beverage industry as acidulants and preservatives, while also serving as versatile precursors for industrially relevant compounds. Fumaric acid is still predominantly produced through petroleum-derived processes. To enhance production efficiency and diversify supply, we are engineering Kluyveromyces marxianus as a biosynthetic platform from renewable feedstocks. In previous work, we have established K. marxianus Y-1190 as a host for lactose valorization based on its high growth rate on lactose and its tolerance for acid conditions. Here, we establish a trifunctional genome-wide library for K. marxianus using CRISPR activation, interference, and deletion to allow identification of gene expression perturbations that enhance tolerance to fumaric acid. We determined that deletion of ATP7, encoding a subunit of the mitochondrial F1F0 ATP synthase, and overexpression of QDR2 and QDR3, two previously uncharacterized members of the 12-spanner H+ antiporter (DHA1) family in K. marxianus, can enhance fumaric acid tolerance. We also found that integrated overexpression of both QDR2 and QDR3 in a ?FUM1 background strain improved titers of fumaric acid production from 0.26 to 2.16 g L-1. Together, these results highlight roles for membrane transport and mitochondrial function in enabling fumaric acid tolerance and production in K. marxianus.





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