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Engineering the oleaginous yeast Yarrowia lipolytica for β-farnesene overproduction. 2021

Tianqiong Shi, and Yawen Li, and Li Zhu, and Yangyang Tong, and Junjie Yang, and Yunming Fang, and Meng Wang, and Jieze Zhang, and Yu Jiang, and Sheng Yang
School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People's Republic of China.

β-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 β-farnesene synthase and disruption of the competition pathway. The resulting β-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 β-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 β-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.

UI MeSH Term Description Entries
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D012717 Sesquiterpenes Fifteen-carbon compounds formed from three isoprenoid units with general formula C15H24. Farnesanes,Farnesene,Farnesenes,Sesquiterpene,Sesquiterpene Derivatives,Sesquiterpenoid,Sesquiterpenoids,Derivatives, Sesquiterpene
D060847 Metabolic Engineering Methods and techniques used to genetically modify cells' biosynthetic product output and develop conditions for growing the cells as BIOREACTORS. Engineering, Metabolic
D025062 Yarrowia A genus of ascomycetous yeast in the family Dipodascaceae, order SACCHAROMYCETALES. Yarrowia lipolytica,Yarrowias

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