Computational biology predicts metabolic engineering targets for increased production of 103 valuable chemicals in yeast

I Iván Domenzain (Department of Life Sciences, Chalmers University of Technology) Y Yao Lu H Haoyu Wang J Junling Shi (Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwstern Polytechnical University) H Hongzhong Lu (State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiao Tong University) J Jens Nielsen

Abstract

Development of efficient cell factories that can compete with traditional chemical production processes is complex and generally driven by case-specific strategies, based on the product and microbial host of interest. Despite major advancements in the field of metabolic modeling in recent years, prediction of genetic modifications for increased production remains challenging. Here, we present a computational pipeline that leverages the concept of protein limitations in metabolism for prediction of optimal combinations of gene engineering targets for enhanced chemical bioproduction. We used our pipeline for prediction of engineering targets for 103 different chemicals using Saccharomyces cerevisiae as a host. Furthermore, we identified sets of gene targets predicted for groups of multiple chemicals, suggesting the possibility of rational model-driven design of platform strains for diversified chemical production.

Article Details

Volume / Issue Vol. 122, Issue 9
Published March 04, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (6)

I

Iván Domenzain

Department of Life Sciences, Chalmers University of Technology

Y

Yao Lu

H

Haoyu Wang

J

Junling Shi

Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwstern Polytechnical University

H

Hongzhong Lu

State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiao Tong University

J

Jens Nielsen