Caffeic acid phenethyl ester (CAPE) is an ester of a hydroxycinnamic acid (phenylpropanoid) and a phenylethanoid (2-phenylethanol; 2-PE), which has long been used in traditional medicine. Here, we synthesized 54 hydroxycinnamic acid-phenylethanoid esters by feeding 64 combinations of hydroxycinnamic acids and phenylethanols to Escherichia coli harboring the rice genes OsPMT and Os4CL. The same approach was applied for ester synthesis with caffeic acid and eight different phenyl alcohols. Two hydroxycinnamoyl phenethyl esters, p-coumaroyl tyrosol and CAPE, were also synthesized from glucose using engineered E. coli by introducing genes for the synthesis of substrates. Consequently, we synthesized approximately 393.4 mg/L p-coumaroyl tyrosol and 23.8 mg/L CAPE with this approach. Overall, these findings demonstrate that the rice PMT and 4CL proteins can be used for the synthesis of diverse hydroxycinnamoyl phenylethanoid esters owing to their promiscuity and that further exploration of the biological activities of these compounds is warranted.
The enzyme, 4-coumarate:CoA ligase (4CL) catalyzes theconversion of 4-coumaric acid into coumaroyl-CoA and afew related substrates into their corresponding products suchas cinnamoyl-CoA, caffeoyl-CoA, and feruloyl-CoA in a pro-cess utilizing ATP and thus channels the common, phenyl-alanine-derived building block into the widely distinct branchesof general phenylpropanoid metabolism.
Plant-derived phenolic compounds, such as hydroxytyrosol and hydroxysalidroside, have a beneficial impact on human health owing to their antioxidant activity. In this study, we used Escherichia coli to synthesize hydroxytyrosol. Tyrosine decarboxylase from Papaver somniferum, tyrosine oxidase from Micrococcus luteus, and 4-hydroxyphenylacetate 3-monooxygenase from E. coli were transformed into the bacterial cell. The resulting transformant successfully synthesized hydroxytyrosol. Furthermore, we used the engineered E. coli strains to synthesize ~ 268.3 mg/L hydroxytyrosol. Three uridine diphosphate-dependent glycosyltransferases (UGTs), which were previously shown to convert tyrosol into salidroside, were tested to synthesize hydroxysalidroside, and one of UGTs was used to synthesize hydroxysalidroside from hydroxytyrosol. Finally, E. coli harboring this UGT converted approximately 50% of hydroxytyrosol into hydroxysalidroside.
Abstract Resveratrol is a typical plant phenolic compound whose derivatives are synthesized through hydroxylation, O -methylation, prenylation, and oligomerization. Resveratrol and its derivatives exhibit anti-neurodegenerative, anti-rheumatoid, and anti-inflammatory effects. Owing to the diverse biological activities of these compounds and their importance in human health, this study attempted to synthesize five resveratrol derivatives (isorhapontigenin, pterostilbene, 4-methoxyresveratrol, piceatannol, and rhapontigenin) using Escherichia coli . Two-culture system was used to improve the final yield of resveratrol derivatives. Resveratrol was synthesized in the first E. coli cell that harbored genes for resveratrol biosynthesis including TAL (tyrosine ammonia lyase), 4CL (4-coumaroyl CoA ligase), STS (stilbene synthase) and genes for tyrosine biosynthesis such as aroG (deoxyphosphoheptonate aldolase) and tyrA (prephenate dehydrogenase). Thereafter, culture filtrate from the first cell was used for the modification reaction carried out using the second E. coli harboring hydroxylase and/or O -methyltransferase. Approximately, 89.8 mg/L of resveratrol was synthesized and using the same, five derivatives were prepared with a conversion rate of 88.2% to 22.9%. Using these synthesized resveratrol derivatives, we evaluated their anti-inflammatory activity. 4-Methoxyresveratrol, pterostilbene and isorhapontigenin showed the anti-inflammatory effects without any toxicity. In addition, pterostilbene exhibited the enhanced anti-inflammatory effects for macrophages compared to resveratrol.
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