Structural, functional and evolutionary diversity of 4-coumarate-CoA ligase in plants

Abstract

The 4-coumarate-CoA ligases (4CL) contribute in channelizing flux of different phenylpropanoid biosynthetic pathways. Expression of 4CL is optimized at developmental stages and in response to environmental triggers such as biotic and abiotic stresses. The enzyme is valuable in metabolic pathway engineering for curcuminoids, resveratrol, biofuel production and nutritional improvement. Vigorous analysis of regulation at functional and expression level is obligatory to attain efficient commercial production of candidate metabolites using 4CL. Phenylpropanoid pathway provides precursors for numerous secondary metabolites in plants. In this pathway, 4-coumarate-CoA ligase (EC 6.2.1.12, 4CL) is the main branch point enzyme which generates activated thioesters. Being the last enzyme of three shared common steps in general phenylpropanoid pathway, it contributes to channelize precursors for different phenylpropanoids. In plants, 4CL enzymes are present in multiple isoforms and encoded by small gene family. It belongs to adenylate-forming enzyme family and catalyzes the reaction that converts hydroxy or methoxy cinnamic acid derivatives to corresponding thioesters. These thioesters are further utilized for biosynthesis of phenylpropanoids, which are known for having numerous nutritional and medicinal applications. In addition, the 4CL enzymes have been characterized from various plants for their role in plant physiology or in biotic and abiotic stresses. Furthermore, specific isoforms are differentially regulated upon exposure to diverse stimuli leading to flux diversion toward the particular metabolite biosynthesis. Evolutionary studies showed that 4CL separately evolved after monocot and dicot segregation. Here, we provide a comprehensive review on 4CL, which includes evolution, function, gene/protein structure, role in metabolite biosynthesis and cellular partition, and their regulation. Based on the available data, we have explored the scope for pathway engineering by utilizing 4CL enzymes.

Global Gene Responses of Resistant and Susceptible Sugarcane Cultivars to Acidovorax avenae subsp. avenae Identified Using Comparative Transcriptome Analysis

“…A number of compounds containing a phenylalanine/tyrosine skeleton are directly or indirectly generated by the phenylpropanoid biosynthesis pathway, which plays various physiological functions in plants including phytoalexin-mediated defenses against herbivores and pathogens [46,47]. Of the first three enzymatic reactions with PAL, C4H (belonging to the CYP73A subfamily of the cytochrome P450-dependent monooxygenase superfamily) and 4CL, which is involved in the general phenylpropanoid pathway, are key enzymes that contribute to production of different phenylpropanoid precursors [47]. The expression of 4CL is altered in response to biotic stresses, reflecting its significant role in counteracting various biotic stresses [47].…”

“…Of the first three enzymatic reactions with PAL, C4H (belonging to the CYP73A subfamily of the cytochrome P450-dependent monooxygenase superfamily) and 4CL, which is involved in the general phenylpropanoid pathway, are key enzymes that contribute to production of different phenylpropanoid precursors [47]. The expression of 4CL is altered in response to biotic stresses, reflecting its significant role in counteracting various biotic stresses [47]. Furthermore, peroxidase functions in the last step of lignin biosynthesis [48].…”

Plant Fibers and Phenolics: A Review on Their Synthesis, Analysis and Combined Use for Biomaterials with New Properties

“…Mutations in ANS cause yellow pigmentation, as observed in yellow raspberry fruits, where a 5 bp insertion in the coding region was associated to the observed phenotype [44]. 4CL is the last enzyme intervening in the three shared steps of the general phenylpropanoid pathway and as such it channels activated thioesters of hydroxycinnamic acids to the synthesis of different phenylpropanoids [39]. Several 4CL genes are present in plants, they respond to environmental cues and phytohormones and are classified in type I and II: The first ones are related to lignin biosynthesis, while the latter are related to the synthesis of phenylpropanoids other than lignin [39].…”

“…4CL is the last enzyme intervening in the three shared steps of the general phenylpropanoid pathway and as such it channels activated thioesters of hydroxycinnamic acids to the synthesis of different phenylpropanoids [39]. Several 4CL genes are present in plants, they respond to environmental cues and phytohormones and are classified in type I and II: The first ones are related to lignin biosynthesis, while the latter are related to the synthesis of phenylpropanoids other than lignin [39]. In thale cress, different 4CL isoforms are implicated in the shunting of the metabolic flux: AtCL1 is co-expressed with lignin biosynthetic genes, while AtCL3 with flavonoid biosynthetic ones [39].…”

Characterization of the Gh4CL gene family reveals a role of Gh4CL7 in drought tolerance

“…The 4-coumarate-CoA ligase (EC 6.2.1.12, 4CL) is the main branch point enzyme of the phenylpropanoid pathway, which catalyzes cinnamic acid to generate corresponding CoA thioesters [8]. Products of 4CL subsequently serve as substrates of various oxygenases, reductases and transferases for biosynthesis of lignin, flavonoids, anthocyanins, aurones, stilbenes, coumarins, suberin, cutin, sporopollenin, and others [9,10]. The 4CL gene family has been characterized in many plants, such as Arabidopsis [11], rice [12,13], soybean [14] and aspen [15,16].…”