BibTex format
@article{Sun:2026:10.1016/j.synbio.2025.08.011,
author = {Sun, T and Sun, M-L and Lin, L and Gao, J and Ledesma-Amaro, R and Wang, K and Ji, X-J},
doi = {10.1016/j.synbio.2025.08.011},
journal = {Synthetic and Systems Biotechnology},
pages = {48--58},
title = {Combining multiplex metabolic engineering with adaptive evolution strategies for high-level succinic acid production in Yarrowia lipolytica},
url = {http://dx.doi.org/10.1016/j.synbio.2025.08.011},
volume = {11},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Succinic acid, an essential platform chemical with extensive utility in biodegradable materials, pharmaceuticals, and the food industry, faces challenges of high energy consumption and environmental pollution in traditional chemical synthesis. Here, we employed multiplex metabolic engineering and adaptive laboratory evolution to enhance succinic acid biosynthesis in Yarrowia lipolytica. By attenuating succinate dehydrogenase (Sdh) activity, mitigating by-product accumulation, and enhancing the succinate synthesis pathway, engineered strains showed efficient succinic acid production from glycerol. The titer reached 130.99 g/L under unregulated pH conditions, translating to a yield of 0.35 g/g and a productivity of 0.70 g/(L·h). Subsequently, transporter engineering and adaptive evolution strategies were applied to enhance glucose utilization for succinic acid synthesis, yielding an evolved strain that eliminated the growth lag phase and produced 106.68 g/L succinic acid from glucose, which translated to a yield of 0.32 g/g and a productivity of 0.64 g/(L·h). Additionally, transcriptomic analysis and inverse metabolic engineering revealed that 4-hydroxyphenylpyruvate dioxygenase (4-Hppd) in the tyrosine degradation pathway partially restored the growth of Sdh-deficient strains on glucose, offering new insights for subsequent succinic acid biomanufacturing using Y. lipolytica.
AU - Sun,T
AU - Sun,M-L
AU - Lin,L
AU - Gao,J
AU - Ledesma-Amaro,R
AU - Wang,K
AU - Ji,X-J
DO - 10.1016/j.synbio.2025.08.011
EP - 58
PY - 2026///
SN - 2405-805X
SP - 48
TI - Combining multiplex metabolic engineering with adaptive evolution strategies for high-level succinic acid production in Yarrowia lipolytica
T2 - Synthetic and Systems Biotechnology
UR - http://dx.doi.org/10.1016/j.synbio.2025.08.011
UR - https://www.sciencedirect.com/science/article/pii/S2405805X2500122X?via%3Dihub
VL - 11
ER -