期刊
BIOTECHNOLOGY JOURNAL
卷 16, 期 7, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/biot.202100097
关键词
DAG acyltransferase; fatty acid biosynthesis; metabolic engineering; Yarrowia lipolytica; β ‐ farnesene
资金
- National Science Fund for Distinguished Young Scholars [21825804]
- National Natural Science Foundation of China [21636003, 21878142]
- Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project [TSBICIP-PTJS-003-04]
- PostgraduateResearch& Practice Innovation Program of Jiangsu Province [KYCX19_0866]
The study successfully engineered Yarrowia lipolytica to increase the production of beta-farnesene and further boosted the yield by knocking out acyltransferase genes. Additionally, fed-batch fermentation significantly enhanced the beta-farnesene titer, providing a new route for producing other terpenoids more efficiently.
beta-farnesene is a sesquiterpenoid with various industrial applications which is now commercially produced by a Saccharomyces cerevisiae strain obtained by random mutagenesis and genetic engineering. We rationally designed a genetically defined Yarrowia lipolytica through recovery of L-leucine biosynthetic route, gene dosage optimization of beta-farnesene synthase and disruption of the competition pathway. The resulting beta-farnesene titer was improved from 8 to 345 mg L-1. Finally, the strategy for decreasing the lipid accumulation by individually and iteratively knocking out four acyltransferases encoding genes was adopted. The result displayed that beta-farnesene titer in the engineered strain CIBT6304 in which acyltransferases (DGA1 and DGA2) were deleted increased by 45% and reached 539 mg L-1 (88 mg g(-1) DCW). Using fed-batch fermentation, CIBT6304 could produce the highest beta-farnesene titer (22.8 g L-1) among the genetically defined strains. This study will provide the foundation of engineering Y. lipolytica to produce other terpenoids more cost-efficiently.
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