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Improved campesterol production in engineered Yarrowia lipolytica strains
Yu Zhang1,2, Ying Wang1,2, Mingdong Yao1,2
1Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, 92 Weijin Road, Tianjin, 300072, China.
Biotechnology Letters
|March 31, 2017
Summary
This study engineered Yarrowia lipolytica to enhance campesterol production, a crucial steroid precursor. The engineered yeast achieved a high yield of 942 mg/l, establishing a promising platform for pharmaceutical steroid synthesis.
Area of Science:
- Biotechnology
- Synthetic Biology
- Metabolic Engineering
Background:
- Campesterol is a vital precursor for synthesizing pharmaceutical steroids.
- Yarrowia lipolytica is a robust yeast platform for microbial production of valuable compounds.
Purpose of the Study:
- To engineer Yarrowia lipolytica for improved heterologous production of campesterol.
- To establish an efficient platform for synthesizing steroid drug precursors.
Main Methods:
- Screening of 7-dehydrocholesterol reductase (DHCR7) from various species.
- Genetic engineering of Yarrowia lipolytica, including overexpression of ACL and POX2.
- High cell density fermentation in a bioreactor using sunflower seed oil as a carbon source.
Main Results:
- The DHCR7 from Danio rerio was identified as the optimal enzyme for campesterol synthesis.
- Overexpression of ATP: citrate lyase (ACL) or peroxisome acyl-CoA oxidase 2 (POX2) significantly enhanced campesterol production.
- A maximum campesterol yield of 942 mg/l was achieved with the POX2-overexpressing strain.
Conclusions:
- A viable Yarrowia lipolytica-based platform for campesterol synthesis was successfully established.
- The study provides efficient strategies for enhancing the production of target molecules in Y. lipolytica.
- High oil utilization efficiency was demonstrated for the engineered yeast strain.