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

Iván Domenzain, Yao Lu, Haoyu Wang, Junling Shi, Hongzhong Lu, Jens Nielsen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere2417322122
JournalProceedings of the National Academy of Sciences of the United States of America
Volume122
Issue number9
DOIs
StatePublished - 4 Mar 2025

Keywords

  • genome scale modeling
  • metabolic engineering
  • synthetic biology
  • yeast

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