Uncovering and Correcting the Effect of Biomass Molecular Weight Discrepancies in FBA Calculations

In genome-scale metabolic models, the biomass has by definition a molecular weight of 1 g mmol-1. This is critical for correctly predicting growth yields, contrasting multiple models and more importantly modeling microbial communities. Nevertheless, we identified significant departures after examining 64 published models. The biomass weights of 34 models differed by 5 – 50%, while 8 models have discrepancies >50%. 20 models were manually curated. By maximizing the original vs. corrected biomass reactions, flux balance analysis revealed >10% differences in growth yields for 12 of the curated models. Biomass molecular weight discrepancies are accentuated in microbial community simulations as they can cause significant and systematic errors in the community composition. Microbes with underestimated biomass molecular weights are overpredicted in the community whereas microbes with overestimated biomass weights are underpredicted. The observed departures in community composition are disproportionately larger than the discrepancies in the biomass weight estimate. Here we introduce a systematic procedure for checking and correcting the biomass weight, which we propose as a standard practice for metabolic reconstructions.