BioChem - DOS

Iterative integration of multiple-copy pathway genes in Yarrowia lipolytica for heterologous β-carotene production

Metabolic engineering

Gao, Shuliang; Tong, Yangyang; Zhu, Li; Ge, Mei; Zhang, Yian; Chen, Daijie; Jiang, Yu; Yang, Sheng

<P><B>Abstract</B></P> <P>&beta;-Carotene is a terpenoid molecule with high hydrophobicity that is often used as an additive in foods and feed. Previous work has demonstrated the heterologous biosynthesis of &beta;-carotene from an intrinsic high flux of acetyl-CoA in 12 steps through 11 genes in <I>Yarrowia lipolytica</I>. Here, an efficient biosynthetic pathway capable of producing 100-fold more &beta;-carotene than the baseline construct was generated using strong promoters and multiple gene copies for each of the 12 steps. Using fed-batch fermentation with an optimized medium, the engineered pathway could produce 4g/L &beta;-carotene, which was stored in lipid droplets within engineered <I>Y. lipolytica</I> cells. Expansion of these cells for squalene production also demonstrated that <I>Y. lipolytica</I> could be an industrially relevant platform for hydrophobic terpenoid production.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The first time engineering <I>Yarrowia lipolytica</I> for heterologous &beta;-carotene synthesis. </LI> <LI> &beta;-carotene production titer achieved in this study is the highest level so far. </LI> <LI> <I>Y. lipolytica</I> has the potential to serve as an excellent host for hydrophobic terpenoids production. </LI> </UL> </P>

2017

Elsevier

1096-7176

1096-7184

41

pp.192-201

10.1016/j.ymben.2017.04.004

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART77882525

Yarrowia lipolytica; Metabolic engineering; β-carotene; Terpenoid