Heterologous Production of Curcuminoids

Abstract

SUMMARY Curcuminoids, components of the rhizome of turmeric, show several beneficial biological activities, including anticarcinogenic, antioxidant, anti-inflammatory, and antitumor activities. Despite their numerous pharmaceutically important properties, the low natural abundance of curcuminoids represents a major drawback for their use as therapeutic agents. Therefore, they represent attractive targets for heterologous production and metabolic engineering. The understanding of biosynthesis of curcuminoids in turmeric made remarkable advances in the last decade, and as a result, several efforts to produce them in heterologous organisms have been reported. The artificial biosynthetic pathway (e.g., in Escherichia coli ) can start with the supplementation of the amino acid tyrosine or phenylalanine or of carboxylic acids and lead to the production of several natural curcuminoids. Unnatural carboxylic acids can also be supplemented as precursors and lead to the production of unnatural compounds with possibly novel therapeutic properties. In this paper, we review the natural conversion of curcuminoids in turmeric and their production by E. coli using an artificial biosynthetic pathway. We also explore the potential of other enzymes discovered recently or already used in other similar biosynthetic pathways, such as flavonoids and stilbenoids, to increase curcuminoid yield and activity.

A Combinatorial Approach to Optimize the Production of Curcuminoids From Tyrosine in Escherichia coli

“…A possible reason for this is the low availability of the precursor malonyl-CoA (Xu et al, 2012(Xu et al, , 2013Machado et al, 2014;Lv et al, 2019) that is naturally synthesized in E. coli for the production of fatty acids and phospholipids and that is also needed for the production of curcuminoids (Figure 1). Therefore, in the future, to achieve high concentrations of curcumin from ferulic acid it will be important to also increase malonyl-CoA availability using well-established methods (Xu et al, 2012(Xu et al, , 2013Rodrigues et al, 2015c;Jones et al, 2017;Fang et al, 2018;Lv et al, 2019).…”

Optimization of fermentation conditions for the production of curcumin by engineered Escherichia coli

“…Acetate, which is a growth inhibitor, accumulates less in E. coli BL21 because this strain presents a higher expression of acetyl-CoA synthetase during the glucose exponential phase [25]. This enzyme converts acetate to acetyl-CoA, which in turn is converted to malonyl-CoA, whose availability in the cell is very important for curcumin production [6]. The comparison of these production results also suggests that our pathway, which consisted of 4CL1 from Arabidopsis thaliana and DCS and CURS1 from C. longa, is more efficient than the pathway described by Katsuyama et al [10], which consisted of 4CL from Lithospermum erythrorhizon, CUS and overexpression of acetyl-CoA carboxylase from E. coli.…”

The ameliorative effect of curcumin extract on the morphological and skeletal abnormalities induced by sunset yellow and tartrazine in the developing chick embryo Gallus domesticus

“…The Joint FAO/WHO Expert Committee on Food Additives (JECFA) allocated an acceptable daily intake (ADI) of Cur is 0-3 mg/kg bw/day (EFSA, 2010;Amalraj et al, 2017). FDA have been proved curcuminoids as" Generally Recognized as Safe" (GRAS) when used in a suitable dose (Rodrigues et al, 2015;Hewlings and Kalman, 2017). Cur has several therapeutic properties such as antioxidant (Alsamydai and Jaber, 2018).…”