Host and Pathway Engineering for Enhanced Lycopene Biosynthesis in Yarrowia lipolytica

Area of Science:

• Biotechnology
• Metabolic Engineering
• Industrial Microbiology

Background:

• Carotenoids are commercially valuable molecules used as food additives and nutraceuticals.
• Current petrochemical-based synthesis is unsustainable; bioproduction from renewable resources offers an eco-friendly alternative.
• Yarrowia lipolytica is an oleaginous yeast chassis suitable for microbial production of valuable compounds.

Purpose of the Study:

• To engineer the yeast Yarrowia lipolytica for enhanced bioproduction of the carotenoid lycopene.
• To identify and implement strategies for improving lycopene yield and titer in Y. lipolytica.
• To advance the understanding of carotenoid biosynthesis pathways in engineered yeast.

Main Methods:

• Genetic engineering of Yarrowia lipolytica to introduce and optimize carotenoid biosynthesis genes.
• Overexpression of key enzymes in the mevalonate pathway (e.g., HMG1, MVD1).
• Alleviation of auxotrophic mutations (leucine and uracil biosynthesis) in the host strain.
• Cultivation of engineered strains in bioreactors to assess lycopene production.

Main Results:

• Engineered Y. lipolytica produced lycopene from renewable carbon sources.
• Combined strategies of mevalonate pathway overexpression and alleviating auxotrophies significantly enhanced lycopene titer.
• The optimized strain, overexpressing eight genes, achieved a lycopene production of 21.1 mg/g dry cell weight (DCW).
• Specific gene targets included HMG1, CrtI, MVD1, EGR8, CrtB, and CrtE.

Conclusions:

• Successful engineering of Y. lipolytica for high-titer lycopene bioproduction was achieved.
• Optimizing host cell metabolism and biosynthetic pathways is crucial for efficient carotenoid production.
• This study provides valuable insights into carotenoid biosynthesis in Y. lipolytica, paving the way for future metabolic engineering efforts.