Background
Saccharomyces cerevisiae is a widely used microorganism in biotechnology, serving as a cell factory for the production of diverse high-value chemicals. Fatty acid catabolism, particularly β-oxidation, plays a pivotal role in degrading fatty acids and producing acyl-CoA intermediates, which are precursors for numerous valuable compounds (Wang et al., 2024). In S. cerevisiae, β-oxidation occurs exclusively in peroxisomes and is essential for both fatty acid degradation and the metabolic engineering of pathways to accumulate medium-chain acyl-CoAs, precursors for the biosynthesis of high-value chemicals such as capsaicinoids (Muratovska et al., 2022).
Engineering β-oxidation pathways has significant potential to expand substrate specificity and generate a broader diversity of medium-chain acyl-CoAs. This can be achieved by integrating heterologous enzymes with promiscuous substrate specificity or optimized catalytic properties. These tailored acyl-CoAs could subsequently feed into engineered metabolic pathways for novel or improved production of industrially and pharmaceutically relevant compounds.
In this project, we aim to develop a comprehensive database of β-oxidation enzymes from microbial species known to produce medium-chain fatty acids. To achieve this, we will:
- Identify microbial species known for their β-oxidation capabilities and medium-chain fatty acid production by conducting a literature search, including yeast species closely related to cerevisiae.
- Download and annotate the genomes of selected species to identify β-oxidation genes to build a database of β-oxidation enzymes.
- Perform comparative analyses of β-oxidation pathways and enzyme sequences to identify conserved motifs or residues critical for substrate recognition and specificity.
- Map and compare β-oxidation pathways across species to uncover unique strategies for fatty acid catabolism and identify candidate enzymes for heterologous expression in cerevisiae.
This study will provide insights into the molecular determinants of enzyme specificity and pathway diversity, enabling the rational design of β-oxidation pathways in S. cerevisiae. Ultimately, it will support the engineering of yeast strains capable of efficiently producing medium-chain acyl-CoAs for applications in biotechnology and synthetic biology.
Specific aims
- Build a database of enzymes involved in β-oxidation for the production of medium-chain fatty acids
- Perform comparative analysis of the identified enzymes to improve the production of medium-chain acyl-coA.
Contact
Dr. Ghjuvan Grimaud (Division of Biotechnology and Applied Microbiology)
ghjuvan_micaelu.grimaud@ple.lth.se
References
Muratovska, N., Silva, P., Pozdniakova, T., Pereira, H., Grey, C., Johansson, B., & Carlquist, M. (2022). Towards engineered yeast as production platform for capsaicinoids. Biotechnology Advances, 59, 107989.
Wang, Z., Su, C., Zhang, Y., Shangguan, S., Wang, R., & Su, J. (2024). Key enzymes involved in the utilization of fatty acids by Saccharomyces cerevisiae: a review. Frontiers in Microbiology, 14, 129418