Genetic and bioprocess engineering to improve squalene production in Yarrowia lipolytica

TY - JOUR

T1 - Genetic and bioprocess engineering to improve squalene production in Yarrowia lipolytica

AU - Liu, Huan

AU - Wang, Fang

AU - Deng, Li

AU - Xu, Peng

N1 - Publisher Copyright: © 2020 The Authors

PY - 2020/12

Y1 - 2020/12

N2 - Squalene is the precursor for triterpene-based natural products and steroids-based drugs. It has been widely used as pharmaceutical intermediates and personal care products. The aim of this work is to test the feasibility of engineering Yarrowia lipolytica as a potential host for squalene production. The bottleneck of the pathway was removed by overexpressing native HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase. With the recycling of NADPH from the mannitol cycle, the engineered strain produced about 180.3 mg/L and 188.2 mg/L squalene from glucose or acetate minimal media. By optimizing the C/N ratio, controlling the media pH and mitigating acetyl-CoA flux competition from lipogenesis, the engineered strain produced 502.7 mg/L squalene, a 28-fold increase over the parental strain (17.2 mg/L). This work may serve as a baseline to harness Y. lipolytica as an oleaginous cell factory for sustainable production of squalene or terpenoids-based chemicals and natural products.

AB - Squalene is the precursor for triterpene-based natural products and steroids-based drugs. It has been widely used as pharmaceutical intermediates and personal care products. The aim of this work is to test the feasibility of engineering Yarrowia lipolytica as a potential host for squalene production. The bottleneck of the pathway was removed by overexpressing native HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase. With the recycling of NADPH from the mannitol cycle, the engineered strain produced about 180.3 mg/L and 188.2 mg/L squalene from glucose or acetate minimal media. By optimizing the C/N ratio, controlling the media pH and mitigating acetyl-CoA flux competition from lipogenesis, the engineered strain produced 502.7 mg/L squalene, a 28-fold increase over the parental strain (17.2 mg/L). This work may serve as a baseline to harness Y. lipolytica as an oleaginous cell factory for sustainable production of squalene or terpenoids-based chemicals and natural products.

KW - Mannitol cycle

KW - Metabolic engineering

KW - Mevalonate pathway

KW - Oleaginous yeast

KW - Squalene

UR - http://www.scopus.com/inward/record.url?scp=85089424765&partnerID=8YFLogxK

U2 - 10.1016/j.biortech.2020.123991

DO - 10.1016/j.biortech.2020.123991

M3 - 文章

C2 - 32805480

AN - SCOPUS:85089424765

SN - 0960-8524

VL - 317

JO - Bioresource Technology

JF - Bioresource Technology

M1 - 123991

ER -