BioChem - DOS

Metabolic Engineering of Saccharomyces cerevisiae To Overproduce Squalene

Journal of agricultural and food chemistry

Li, Tian; Liu, Guo-Song; Zhou, Wei; Jiang, Min; Ren, Yu-Hong; Tao, Xin-Yi; Liu, Min; Zhao, Ming; Wang, Feng-Qing; Gao, Bei; Wei, Dong-Zhi

<P>Squalene has wide applications in the food and pharmaceutical industries. Engineering microbes to produce squalene is a promising alternative for traditional production approaches. In this study, squalene production was enhanced to 978.24 mg/L through stepwise overexpression of the enzymes that catalyze acetyl-CoA to squalene. Subsequently, to increase the activity of HMG-CoA reductase and alleviate the high dependence on NADPH, the HMG-CoA reductase (NADH-HMGR) from <I>Silicibacter pomeroyi</I>, highly specific for NADH, was introduced, which increased squalene production to 1086.31 mg/L. Native ethanol dehydrogenase <I>ADH2</I> and acetaldehyde dehydrogenase <I>ADA</I> from <I>Dickeya zeae</I> were further overexpressed, which enhanced the capability to utilize ethanol for squalene synthesis and endowed the engineered strain with greater adaptability to high ethanol concentrations. Finally, a remarkable squalene production of 9472 mg/L was obtained from ethanol via carbon source-controlled fed-batch fermentation. This study will greatly accelerate the process of developing microbial cell factories for squalene production.</P><BR>[FIG OMISSION]</BR>

2020

American Chemical Society

0021-8561

1520-5118

68

7

pp.2132-2138

10.1021/acs.jafc.9b07419.s001

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART98898651

https://doi.org/10.1021/acs.jafc.9b07419.s001

Saccharomyces cerevisiae; metabolic engineering; squalene; overproduction; ethanol; carbon source utilization