Formation of Flavonoid Metabolons: Functional Significance of Protein-Protein Interactions and Impact on Flavonoid Chemodiversity

Abstract

Flavonoids are a class of plant specialized metabolites with more than 6,900 known structures and play important roles in plant survival and reproduction. These metabolites are derived from p -coumaroyl-CoA via the sequential actions of a variety of flavonoid enzymes, which have been proposed to form weakly bound, ordered protein complexes termed flavonoid metabolons. This review discusses the impacts of the formation of flavonoid metabolons on the chemodiversity of flavonoids. Specific protein-protein interactions in the metabolons of Arabidopsis thaliana and other plant species have been studied for two decades. In many cases, metabolons are associated with the ER membrane, with ER-bound cytochromes P450 hypothesized to serve as nuclei for metabolon formation. Indeed, cytochromes P450 have been found to be components of flavonoid metabolons in rice, snapdragon, torenia, and soybean. Recent studies illustrate the importance of specific interactions for the efficient production and temporal/spatial distribution of flavonoids. For example, in diverse plant species, catalytically inactive type-IV chalcone isomerase-like protein serves as an enhancer of flavonoid production via its involvement in flavonoid metabolons. In soybean roots, a specific isozyme of chalcone reductase (CHR) interacts with 2-hydroxyisoflavanone synthase, to which chalcone synthase (CHS) can also bind, providing a mechanism to prevent the loss of the unstable CHR substrate during its transfer from CHS to CHR. Thus, diversification in chemical structures and temporal/spatial distribution patterns of flavonoids in plants is likely to be mediated by the formation of specific flavonoid metabolons via specific protein-protein interactions.

Proanthocyanidin Biosynthesis—a Matter of Protection

“…The role of metabolons in reactions specific for PA biosynthesis, as suggested in Figure 2, requires further investigation. It is now well established that the earlier reactions in the flavonoid pathway are organized in metabolons anchored to the endoplasmic reticulum through association with the cytochrome P450 enzymes of the pathway (Nakayama et al, 2019;Waki et al, 2020), but physical interactions between the later enzymes of the pathway have yet to be demonstrated. The need for such physical organization of the pathway would appear necessary to explain the differentiation of starter unit from extension unit synthesis using shared enzymes (Jun et al, 2018).…”

A conserved strategy of chalcone isomerase-like protein to rectify promiscuous chalcone synthase specificity

“…1) 6 . Additionally, CHS, CHI, and other flavonoid enzymes further down the pathway are reportedly organized to form a metabolon (i.e., a fragile, highly organized super-molecular enzyme complex) using P450 protein(s) as a nucleus for the enzyme association [7][8][9][10][11] .…”

“…A diffusible intermediate of the CHS-catalyzed reaction may serve as a substrate of chalcone reductase in deoxyflavonoid biosynthesis 10 . Additionally, THC serves as a precursor of aurones, whereas naringenin serves as a precursor of other flavonoids 6,11 . CL, 4-coumaric acid:CoA ligase.…”

Identification and comparative expression analysis of chalcone synthase, flavanone 3-hydroxylase and dihydroflavonol 4-reductase genes in wild pomegranate (Punica granatum L.) organs

“…Expression profile of flavonoid biosynthetic genes -Previous reports have revealed that flavonoid biosynthesis occurs at specific stages of plant development and is limited to certain tissues (Nakayama et al 2019). This flavonoid accumulation in some plant organs reflects the activity of certain enzymes that function in its biosynthetic pathway (Tohge et al 2017).…”