2015 journal article

4-Coumaroyl and caffeoyl shikimic acids inhibit 4-coumaric acid:coenzyme a ligases and modulate metabolic flux for 3-hydroxylation in monolignol biosynthesis of Populus trichocarpa

Molecular Plant, 8(1), 176–187.

By: C. Lin n, J. Wang n, Q. Li*, H. Chen n, J. Liu n, P. Loziuk n, J. Song n, C. Williams n ...

co-author countries: China 🇨🇳 United States of America 🇺🇸
author keywords: monolignol biosynthesis; Populus trichocarpa; metabolic flux; reaction and inhibition kinetics; LC-MS/MS; 4-coumaroyl and caffeoyl shikimic acids
MeSH headings : Acyl Coenzyme A / metabolism; Coenzyme A Ligases / metabolism; Coumaric Acids / metabolism; Coumaric Acids / pharmacology; Hydroxylation / drug effects; Plant Proteins / metabolism; Populus / drug effects; Populus / enzymology; Populus / metabolism; Propionates; Shikimic Acid / pharmacology
Source: ORCID
Added: April 18, 2019

Downregulation of 4-coumaric acid:coenzyme A ligase (4CL) can reduce lignin content in a number of plant species. In lignin precursor (monolignol) biosynthesis during stem wood formation in Populus trichocarpa, two enzymes, Ptr4CL3 and Ptr4CL5, catalyze the coenzyme A (CoA) ligation of 4-coumaric acid to 4-coumaroyl-CoA and caffeic acid to caffeoyl-CoA. CoA ligation of 4-coumaric acid is essential for the 3-hydroxylation of 4-coumaroyl shikimic acid. This hydroxylation results from sequential reactions of 4-hydroxycinnamoyl-CoA:shikimic acid hydroxycinnamoyl transferases (PtrHCT1 and PtrHCT6) and 4-coumaric acid 3-hydroxylase 3 (PtrC3H3). Alternatively, 3-hydroxylation of 4-coumaric acid to caffeic acid may occur through an enzyme complex of cinnamic acid 4-hydroxylase 1 and 2 (PtrC4H1 and PtrC4H2) and PtrC3H3. We found that 4-coumaroyl and caffeoyl shikimic acids are inhibitors of Ptr4CL3 and Ptr4CL5. 4-Coumaroyl shikimic acid strongly inhibits the formation of 4-coumaroyl-CoA and caffeoyl-CoA. Caffeoyl shikimic acid inhibits only the formation of 4-coumaroyl-CoA. 4-Coumaroyl and caffeoyl shikimic acids both act as competitive and uncompetitive inhibitors. Metabolic flux in wild-type and PtrC3H3 downregulated P. trichocarpa transgenics has been estimated by absolute protein and metabolite quantification based on liquid chromatography–tandem mass spectrometry, mass action kinetics, and inhibition equations. Inhibition by 4-coumaroyl and caffeoyl shikimic acids may play significant regulatory roles when these inhibitors accumulate.