Jianmin Xing, Yilan Liu, Maohua Yang, Qinhong Wang and Yanhe Ma
National Key Lab of Biochemical Engineering, Institute of Process Engineering, CAS, China
Microbial synthesis of fatty alcohols from renewable resources has attracted increasing attentions. However, the low tilters of fatty alcohols hampered its industrialization. Here we designed a novel strategy for fatty alcohol production based on fatty acid starvation. For the first time, all three acyl- ACP thioesterases related to formation of fatty acids were knocked out to enhance fatty alcohol production. The fatty alcohol titer increased about 58%, while fatty acids concentration dropped 73%. Transcriptome analysis showed that expression levels of genes for fatty acid synthesis and glycolysis pathway were upregulated, while fatty acid degradation and TCA pathway were downregulated. Furthermore, Fatty alcohol production was enhanced by deleting the genes responsible for lactate and acetate formation. The optimized strain, E. coli MGL2 with exogenous fatty acyl-ACP reductase, accumulated fatty alcohols at a remarkable level of 6.33 g/L under fed-batch fermentation. This is the highest reported titer of fatty alcohols produced by microorganisms.
Keywords: E. coli, Fatty alcohols, Acyl-ACP thioesterases, Fatty acid starvation.