posted on 2023-12-28, 21:16authored byJianbin Chen, Weigao Wang, Lian Wang, Huijing Wang, MingLong Hu, Jingwen Zhou, Guocheng Du, Weizhu Zeng
Curcumin is a natural phenylpropanoid compound with various
biological
activities and is widely used in food and pharmaceuticals. A de novo curcumin biosynthetic pathway was constructed in Escherichia coli BL21(DE3). Optimization of the curcumin
biosynthesis module achieved a curcumin titer of 26.8 ± 0.6 mg/L.
Regulating the metabolic fluxes of the β-oxidation pathway and
fatty acid elongation cycle and blocking the endogenous malonyl-CoA
consumption pathway increased the titer to 113.6 ± 7.1 mg/L.
Knockout of endogenous curcumin reductase (curA)
and intermediate product detoxification by heterologous expression
of the solvent-resistant pump (srpB) increased the
titer to 137.5 ± 3.0 mg/L. A 5 L pilot-scale fermentation, using
a three-stage pH alternation strategy, increased the titer to 696.2
± 20.9 mg/L, 178.5-fold higher than the highest curcumin titer
from de novo biosynthesis previously reported, thereby
laying the foundation for efficient biosynthesis of curcumin and its
derivatives.