Curcuminoids are natural secondary metabolites from the herb Curcuma longa. Their beneficial
properties, mainly as anti-cancer agents, have been exhaustively reported but the therapeutic
effect of curcumin is limited by its fast systemic elimination along with poor bioavailability.
Besides, curcumin extraction from plants is very expensive and it is hard to synthetize
chemically. For these reasons, the use of microorganisms to produce these remarkable
compounds on large scale and with greater yields constitutes an interesting approach. In the
SYNBIOBACTHER project, the aim of producing curcumin from ferulic acid using an engineered
Escherichia coli was achieved adding three enzymatic steps using plant genes (4-coumarate-CoA
ligase (4CL) from Arabidopsis thaliana; diketide-CoA synthase (DCS) and curcumin synthase 1
(CURS1) from C. longa). The present work aims to improve curcumin production from ferulic acid
by optimizing the production medium and other operational conditions. Previously, we used a
standard two-step fermentation strategy (LB + M9 minimal media) to overcome the metabolic
burden associated with protein overexpression and poor growth observed in minimal medium.
Although feasible at the laboratory scale, the biomass separation is much more difficult,
laborious and expensive in large scale fermentations. Therefore, we intend to develop a single
medium formulation more suitable for the production of curcuminoids. MOPS minimal medium,
TB and also LB and M9 are being evaluated. Furthermore, previously we studied in silico which
gene deletions would enhance the curcumin production by the metabolic engineered E. coli.
Using a recombineering approach, we are implementing those gene knockouts to construct
several E. coli mutants (Δgnd; ΔfumA,fumB,fumC; ΔfumA,fumB,fumC,ccmA;
ΔfumA,fumB,fumC,ccmA,argO) that will produce curcumin from ferulic acid. The curcuminoids
production by these E. coli mutants is being evaluated
