Microbial production of curcumin

Abstract

Curcumin, a polyphenol produced by turmeric (Curcuma longa), has attracted increased attention due to its potential as a novel cancer-fighting drug. However, to satisfy the required curcumin demand for health-related studies, high purity curcumin preparations are required, which are difficult to obtain and are very expensive. Curcumin and other curcuminoids are usually obtained through plant extraction. However, these polyphenols accumulate in low amounts over long periods in the plant and their extraction process is costly and not environmentally friendly. In addition, curcumin chemical synthesis is complex. All these reasons limit the advances in studies related to the in vitro and in vivo curcumin biological activities. The microbial production of curcumin appears as a solution to overcome the limitations associated with the currently used methods. Curcumin biosynthesis begins with the conversion of the aromatic amino acids, phenylalanine and tyrosine, into phenylpropanoids, the curcuminoid precursors. The phenylpropanoids are then activated through condensation with a CoA molecule. Afterwards, curcuminoids are synthesized by the action of type III polyketide synthases (PKS) that combine two activated phenylpropanoids and a malonyl-CoA molecule. To engineer microbes to produce curcumin, the curcuminoid biosynthetic genes must be introduced as microorganisms lack the enzymatic reactions responsible to synthesize curcuminoids. In this chapter, the advances regarding the microbial production of curcumin are exposed. The heterologous production of curcumin has been mainly achieved in the bacteria Escherichia coli. However, other microorganisms have already been explored. Besides the introduction of curcumin biosynthetic genes, the optimization of the microbial chassis must also be considered to maximize the production yields. The strategies employed for this purpose are also herein presented. The maximum titer of curcumin produced by a genetically engineered E. coli was 563.4 mg/L with a substrate conversion yield of 100% from supplemented ferulic acid. Moreover, the de novo production of curcumin was accomplished in E. coli reaching 3.8 mg/L of curcumin. Overall, the recent developments on curcumin heterologous production are very encouraging.