Tracing metabolic flux through time and space with isotope labeling experiments

Authors: Allen, Douglas - Doug; YOUNG, JAMEY - Vanderbilt University

Submitted to: Current Opinion in Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/2019
Publication Date: 8/1/2020
Publication URL: https://handle.nal.usda.gov/10113/6762224
Citation: Allen, D.K., Young, J.D. 2020. Tracing metabolic flux through time and space with isotope labeling experiments. Current Opinion in Biotechnology. 64:92-100. https://doi.org/10.1016/j.copbio.2019.11.003.
DOI: https://doi.org/10.1016/j.copbio.2019.11.003

Interpretive Summary: Ensuring global health and nutrition for future generations will require transformative gains in agricultural productivity and improved strategies to combat disease. At the forefront of challenges that limit success in metabolic engineering and, more generally, restrict our understanding of metabolism are spatial and temporal complexity. Plants grow and metabolism changes over the course of development. Here we discuss the contribution that dynamic studies of metabolism continue to make which can only be measured mechanistically using isotopes that serve to track movement of metabolites. Such studies are important to understand how to engineer plants in a rational way for yield or composition that can help to feed the world and produce renewable feed stocks to meet societal demands.

Technical Abstract: Metabolism is dynamic and must function in context-specific ways to adjust to changes in the surrounding cellular and ecological environment. When isotopic tracers are used, metabolite flow (i.e. metabolic flux) can be quantified through biochemical networks to assess metabolic pathway operation. The cellular activities considered across multiple tissues and organs result in the observed phenotype and can be analyzed to discover emergent, whole-system properties of biology and elucidate misconceptions about network operation. However, temporal and spatial challenges remain significant hurdles and require novel approaches and creative solutions. We survey current investigations in higher plant and animal systems focused on dynamic isotope labeling experiments, spatially resolved measurement strategies, and observations from re-analysis of our own studies that suggest prospects for future work. Related discoveries will be necessary to push the frontier of our understanding of metabolism to suggest novel solutions to cure disease and feed a growing future world population.