Metabolic Modeling of Larvae Resource Allocation for High-Value Fatty Acid Production.

All plant and animal kingdom organisms use highly connected biochemical networks to facilitate sustaining, proliferation, and growth functions. While the biochemical network details are well known, the understanding of the intense regulation principles is still limited. We chose to investigate the fly at the larval stage because this stage is a crucial period for the successful accumulation and allocation of resources for the subsequent organism's developmental stages. We combined iterative wet lab experiments and innovative metabolic modeling design approaches to simulate and explain the larval stage resource allocation processes and biotechnology potential. We performed time-based growth and high-value chemical compound accumulation wet lab chemical analysis experiments on larvae and the Gainesville diet composition. We built and validated the first medium-size, stoichiometric metabolic model to predict the effects of diet-based alterations on fatty acid allocation potential. Using optimization methods such as flux balance and flux variability analysis on the novel insect metabolic model, we predicted that doubled essential amino acid consumption increased the growth rate by 32%, but pure glucose consumption had no positive impact on growth. In the case of doubled pure valine consumption, the model predicted a 2% higher growth rate. In this study, we describe a new framework for researching the impact of dietary alterations on the metabolism of multi-cellular organisms at different developmental stages for improved, sustainable, and directed high-value chemicals.