Combination of a Push–Pull–Block Strategy with a Heterologous Xylose Assimilation Pathway toward Lipid Overproduction from Lignocellulose in Yarrowia lipolytica

Abstract

The production of biodiesel using microbial lipids derived from renewable lignocellulosic biomass is considered a promising strategy to reduce environmental pressure and promote the green energy transition. The hydrolysates of lignocellulosic biomass are rich in glucose and xylose, which makes it crucial to efficiently utilize both sugars. Here, we combined metabolic engineering and adaptive laboratory evolution (ALE) to construct an engineered Yarrowia lipolytica strain that can efficiently produce lipids from glucose and xylose. First, the "Push−Pull−Block" strategy was adopted to increase lipid content to 73.42% of the dry cell weight (DCW). Then, a heterologous xylose-utilization pathway was integrated into the engineered strain, which was subjected to ALE. The final evolved strain could accumulate 53.64% DCW of lipids from xylose, and the lipid titer reached 16.25 g/L. This work sheds light on the potential of microbial lipid overproduction from lignocellulose using engineered Y. lipolytica.

Combination of microbial and chemical synthesis for the sustainable production of β‐elemene, a promising plant‐extracted anticancer compound

“…The oleaginous Yarrowia lipolytica is emerging as an ideal host for hydrophobic sesquiterpene biosynthesis due to its inherent mevalonate (MVA) pathway, high‐throughput acetyl coenzyme A (acetyl‐CoA), and cofactor supply (Park & Ledesma‐Amaro, 2023). It also exhibits outstanding metabolic characteristics, able to metabolize renewable carbon sources and secrete proteins, giving Y. lipolytica unique advantages in the production of a variety of compounds, such as polyketones (Akram et al, 2021), functional sugars (Bilal et al, 2021; Duan et al, 2022), fatty acids (Ledesma‐Amaro & Nicaud, 2016; Sun et al, 2023), and terpenes (Wei et al, 2021; Worland et al, 2020). Moreover, the rapid development of genetic modification tools and technologies has greatly facilitated the application of various engineering strategies for Y. lipolytica (Fordjour et al, 2022; Larroude et al, 2018).…”