PUBLICATION
Improved campesterol production in engineered Yarrowia lipolytica strains
- Authors
- Zhang, Y., Wang, Y., Yao, M., Liu, H., Zhou, X., Xiao, W., Yuan, Y.
- ID
- ZDB-PUB-170331-3
- Date
- 2017
- Source
- Biotechnology Letters 39(7): 1033-1039 (Journal)
- Registered Authors
- Keywords
- 7-Dehydrocholesterol reductase, Campesterol, Metabolic engineering, Oil utilization, Synthetic biology, Yarrowia lipolytica
- MeSH Terms
-
- Recombinant Proteins/genetics
- Recombinant Proteins/metabolism
- Oxidoreductases Acting on CH-CH Group Donors/genetics
- Oxidoreductases Acting on CH-CH Group Donors/metabolism
- Gene Expression
- Bioreactors/microbiology
- Animals
- Yarrowia/genetics*
- Yarrowia/metabolism*
- Cholesterol/analogs & derivatives*
- Cholesterol/biosynthesis
- Phytosterols/biosynthesis*
- Oxidoreductases/genetics
- Oxidoreductases/metabolism
- Biosynthetic Pathways/genetics*
- Metabolic Engineering*
- Zebrafish
- ATP Citrate (pro-S)-Lyase/genetics
- ATP Citrate (pro-S)-Lyase/metabolism
- PubMed
- 28357621 Full text @ Biotechnol. Lett.
Citation
Zhang, Y., Wang, Y., Yao, M., Liu, H., Zhou, X., Xiao, W., Yuan, Y. (2017) Improved campesterol production in engineered Yarrowia lipolytica strains. Biotechnology Letters. 39(7):1033-1039.
Abstract
Objectives To engineer Yarrowia lipolytica for improving the heterologous production of campesterol (a key precursor to manufacture pharmaceutical steroids).
Results By screening 7-dehydrocholesterol reductase (DHCR7) from diverse species, DHCR7 from Danio rerio was the best candidate for campesterol synthesis. Overexpression of ACL (ATP: citrate lyase) or POX2 (peroxisome acyl-CoA oxidase 2) were key to improving campesterol production. The highest yield of campesterol was 942 mg/l was with the strain overexpressing POX2 in a 5 l bioreactor via high cell density fermentation process with a restricted supply of carbon sourc, sunflower seed oil.
Conclusions A promising platform to synthesize downstream steroid drugs was established. Efficient approaches were provided to improve the production of desired molecules in Y. lipolytica with high oil utilization efficiency.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping