bioRxiv Science⌕ Search

Biology subjects

Eliana, E.

Publications and source records attributed to Eliana, E..

2 recordsLinked to original sources

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

Microbial 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 organisms genotype and its environment. This study employs statistical Design of Experiments (DoE) 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 on a 168-fold improvement on pCA titer. 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 bio-process design efforts to unlock the full potential of microbial cell factories.

bioengineering↗

Machine learning-guided optimization of p-coumaric acid production in yeast

Industrial biotechnology uses Design-Build-Test-Learn (DBTL) cycles to accelerate the development of microbial cell factories, required for the transition to a bio-based economy. To use them effectively, appropriate connections between each phase of the cycle are crucial. Using p-coumaric acid production in Saccharomyces cerevisiea as case study, we propose the use of one-pot library generation, random screening, targeted sequencing and machine learning (ML) as links during DBTL cycles. We showed that the robustness and flexibility of ML models strongly enable pathway optimization, and propose feature importance and SHAP values as a guide to expand the design space of original libraries. This approach led to a 68% increased production of p-coumaric acid within two DBTL cycles.

bioengineering↗