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Advances in Lycopene Production: From Natural Sources to Microbial Synthesis Using Yarrowia lipolytica.

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This study engineered yeast for sustainable lycopene production using short-chain fatty acids. Enhanced phospholipid biosynthesis in the yeast boosted lycopene yield, offering a promising alternative to traditional methods.

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Area of Science:

  • Metabolic Engineering
  • Synthetic Biology
  • Biotechnology

Background:

  • Lycopene, a potent antioxidant carotenoid, is valuable for food, pharmaceutical, and cosmetic industries.
  • Conventional lycopene production faces challenges like low yields, high costs, and environmental impact.
  • Microbial cell factories offer a sustainable alternative for carotenoid biosynthesis.

Purpose of the Study:

  • To engineer the oleaginous yeast *Yarrowia lipolytica* for efficient lycopene production.
  • To utilize inexpensive, renewable short-chain fatty acids (SCFAs) as carbon sources.
  • To investigate the role of co-activating phospholipid and carotenoid biosynthesis pathways.

Main Methods:

  • Engineered *Yarrowia lipolytica* by integrating four heterologous genes (*crtI*, *crtB*, *crtE*, *idi*) from *Pantoea agglomerans*.
  • Utilized codon optimization and Golden Gate Assembly for gene integration.
  • Cultivated engineered strains on SCFA media (acetate, butyrate, propionate).

Main Results:

  • Achieved a high lycopene yield of 462.9 mg/g dry cell weight and a titer of 3.41 g/L using butyrate.
  • Identified a strain with enhanced phospholipid biosynthesis (PS05/4lyc/GGA) exhibiting superior lycopene accumulation.
  • Demonstrated that SCFA utilization enhances acetyl-CoA availability and redirects flux towards the mevalonate pathway.

Conclusions:

  • Co-activation of phospholipid and carotenoid biosynthesis pathways is crucial for efficient lycopene accumulation in yeast.
  • Engineered *Y. lipolytica* using SCFAs provides a sustainable and high-yield platform for lycopene production.
  • Elevated membrane lipid biosynthesis improves metabolic stability and stress tolerance in engineered strains.