Patterns of Metabolite Changes Identified from Large-Scale Gene Perturbations in Arabidopsis Using a Genome-Scale Metabolic Network  

Abstract

Metabolomics enables quantitative evaluation of metabolic changes caused by genetic or environmental perturbations. However, little is known about how perturbing a single gene changes the metabolic system as a whole and which network and functional properties are involved in this response. To answer this question, we investigated the metabolite profiles from 136 mutants with single gene perturbations of functionally diverse Arabidopsis (Arabidopsis thaliana) genes. Fewer than 10 metabolites were changed significantly relative to the wild type in most of the mutants, indicating that the metabolic network was robust to perturbations of single metabolic genes. These changed metabolites were closer to each other in a genome-scale metabolic network than expected by chance, supporting the notion that the genetic perturbations changed the network more locally than globally. Surprisingly, the changed metabolites were close to the perturbed reactions in only 30% of the mutants of the well-characterized genes. To determine the factors that contributed to the distance between the observed metabolic changes and the perturbation site in the network, we examined nine network and functional properties of the perturbed genes. Only the isozyme number affected the distance between the perturbed reactions and changed metabolites. This study revealed patterns of metabolic changes from large-scale gene perturbations and relationships between characteristics of the perturbed genes and metabolic changes.Rational and quantitative assessment of metabolic changes in response to genetic modification (GM) is an open question and in need of innovative solutions. Nontargeted metabolite profiling can detect thousands of compounds, but it is not easy to understand the significance of the changed metabolites in the biochemical and biological context of the organism. To better assess the changes in metabolites from nontargeted metabolomics studies, it is important to examine the changed metabolites in the context of the genome-scale metabolic network of the organism.Metabolomics is a technique that aims to quantify all the metabolites in a biological system (Nikolau and Wurtele, 2007;Nicholson and Lindon, 2008;

HEAT INDUCIBLE LIPASE1 Remodels Chloroplastic Monogalactosyldiacylglycerol by Liberating α-Linolenic Acid in Arabidopsis Leaves under Heat Stress

“…Recent metabolomic studies identified metabolic changes of more than 100 Arabidopsis mutants (Hur et al, 2013;Fukushima et al, 2014;Kim et al, 2015). In this study, we focused on glycerolipid accumulation and assessed genetic function under short-term heat stress.…”

How close are we to complete annotation of metabolomes?

“…to encourage the community to focus their metabolite identification efforts on systems we know the most about already (i.e. have species-specific metabolite databases [12–14]), that have sequenced genomes (hence can create genome-wide metabolic reconstructions to predict metabolism; [15]), and that when the metabolomes are successfully identified this knowledge will be of greatest value to the community [10]. The two primary aims of the MOM task group are to integrate disparate model organism-focused research groups into an interactive community, and to share, discuss and develop the analytical and bioinformatics strategies to progress the identification of model organism metabolomes, resulting in best practice documents.…”

Integrative omics of Lonicera japonica Thunb. Flower development unravels molecular changes regulating secondary metabolites

“…In Catharanthus roseus the correlation between hormone metabolism and indole alkaloid biosynthesis was revealed through gene-to-gene and gene-to-metabolite networks [19]. Furthermore, Kim et al [20] revealed the patterns of metabolic changes from large-scale gene regulations and relationships between these regulated genes and metabolic changes. Although secondary metabolites possess important role in normal plant growth and development [21], the enormous biosynthetic potential of secondary metabolites in plant cells still remains unexploited.…”