Combinatorial optimization of pathway, process and media for the production of p‐coumaric acid by Saccharomyces cerevisiae

Author:

Moreno‐Paz Sara1ORCID,van der Hoek Rianne2,Eliana Elif1,Martins dos Santos Vitor A. P.3,Schmitz Joep2,Suarez‐Diez Maria1ORCID

Affiliation:

1. Laboratory of Systems and Synthetic Biology Wageningen University & Research Wageningen The Netherlands

2. Department of Science and Research–dsm‐firmenich, Science & Research Delft The Netherlands

3. Bioprocess Engineering Group Wageningen University & Research Wageningen The Netherlands

Abstract

AbstractMicrobial cell factories are instrumental in transitioning towards a sustainable bio‐based economy, offering alternatives to conventional chemical processes. However, fulfilling their potential requires simultaneous screening for optimal media composition, process and genetic factors, acknowledging the complex interplay between the organism's genotype and its environment. This study employs statistical design of experiments to systematically explore these relationships and optimize the production of p‐coumaric acid (pCA) in Saccharomyces cerevisiae. Two rounds of fractional factorial designs were used to identify factors with a significant effect on pCA production, which resulted in a 168‐fold variation in pCA titre. Moreover, a significant interaction between the culture temperature and expression of ARO4 highlighted the importance of simultaneous process and strain optimization. The presented approach leverages the strengths of experimental design and statistical analysis and could be systematically applied during strain and bioprocess design efforts to unlock the full potential of microbial cell factories.

Funder

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Horizon 2020 Framework Programme

Publisher

Wiley

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