Constructing the metabolic network of wheat kernels based on structure-guided chemical modification and multi-omics data

Metabolic network construction plays a pivotal role in unraveling the regulatory mechanism of biological activities, although it often proves to be challenging and labor-intensive, particularly with non-model organisms. In this study, we develop a computational approach that employs reaction models based on structure-guided chemical modification and related compounds to construct a metabolic network in wheat. This construction results in a comprehensive structure-guided network, including 625 identified metabolites and additional 333 putative reactions compared to the KEGG database. Using a combination of gene annotation, reaction classification, structure similarity, and transcriptome and metabolome analysis correlations, a total of 229 potential genes related to these reactions are identified within this network. To validate the network, the functionality of a hydroxycinnamoyltransferase (TraesCS3D01G314900) for the synthesis of polyphenols and a rhamnosyltransferase (TraesCS2D01G078700) for the modification of flavonoids are verified through in vitro enzymatic studies and wheat mutant tests, respectively. Our research thus supports the utility of structure-guided chemical modification as an effective tool in identifying causal candidate genes for constructing metabolic networks and further in metabolomic genetic studies.