Curcumin biosynthesis from ferulic acid by engineered Saccharomyces cerevisiae

Abstract

Background and Goal: Curcumin is a polyphenolic compound found in Curcuma longa.This bioactive molecule has several reported health-benefit effects, being the anticarcinogenic activity among the most promising ones. However, curcumin extraction from natural sources is hampered by impure products obtained from harsh chemicals and limited by plant seasonality and high prices. Therefore, curcumin heterologous production emerged as an interesting alternative. Escherichia coli has been explored as chassis but the implementation of the pathway in Saccharomyces cerevisiae can have several advantages, including its generally regarded as safe status. Hence, S. cerevisiae was engineered for the first time to produce curcumin from its precursor ferulic acid. Methods and Results:The enzymes 4-coumarate-CoA ligase (4CL1) from Arabidopsis thaliana or feruloyl-CoA synthetase (FerA) from Pseudomonas paucimobilis and type III polyketide synthases (PKSs) from Oryza sativa or C. longa were expressed in BY4741 strain. To avoid ferulic acid deviation, the gene FDC1 coding a ferulic acid decarboxylase was deleted. The maximum curcumin titer was obtained with FerA combined with C. longa PKSs (2.7 mg L −1 ).Conclusions and Implications: Up to our knowledge, this is the first work reporting the expression of a feruloyl-CoA synthase and also curcuminoid biosynthetic enzymes in S. cerevisiae, and consequently, curcumin production.

Heterologous Production of Acrylic Acid: Current Challenges and Perspectives

“…Compared to the glycerol route, this route has the advantage of not needing B 12 vitamin as a cofactor. However, it is well known that malonyl-CoA availability is limited in microorganisms due to tight regulation of fatty acid biosynthesis [88][89][90]. This low availability limits 3-HP production, whereby most of the studies focus on increasing malonyl-CoA concentration, for example, by overexpressing the enzyme acetyl-CoA carboxylase (ACC) [41][42][43]86,87].…”

Microbial Production of Curcumin

“…Recently, Rainha et al (2021a) reported the production of curcumin from ferulic acid in the model yeast Saccharomyces cerevisiae. In this work, two different pathways were tested: the first one composed by 4CL1 from A. thaliana and CUS and the other composed by the same 4CL in combination with DCS and CURS1 from C. longa.…”

A Rehmannia glutinosa caffeic acid O‐methyltransferase functional identification: Reconstitution of the ferulic acid biosynthetic pathway in Saccharomyces cerevisiae using Rehmannia glutinosa enzymes

“…[ 3,4 ] In addition to glycoside compounds such as acteoside and catalpol, R. glutinosa also contains a large group of phenolics with strong biological activity, including ferulic acid (4‐hydroxy‐3‐methoxycinnamic acid, FA). [ 2,5 ] Especially, FA is an important precursor of some medicinal ingredients, such as coumarins, curcuminoids, vanillins, and lignans, [ 5–9 ] which can exhibit a wide range of biomedical effects, including antioxidant, free radical scavenging, anti‐inflammatory, and antiviral activities. [ 5–8 ] As the FA production in plants including R. glutinosa occurs at low efficiency, [ 2,9 ] it is very significant to explore the FA biosynthesis pathways for enhancing the production of FA and its derivations.…”