Integrative Genome-Scale Metabolic Modeling Reveals Versatile Metabolic Strategies for Methane Utilization in Methylomicrobium album BG8

Abstract

A genome-scale metabolic model (GEM) is an integrative platform that enables the incorporation of a wide range of experimental data. It is used to reveal system-level metabolism and, thus, clarify the link between the genotype and phenotype.

Leveraging genome-scale metabolic models to understand aerobic methanotrophs

“…However, GEM models are essentially blind to such paralogous genes as their pathway function is identical, and differences in their primary sequences are usually not easily detected. As an example of paralog blindness, the GEM for M. album BG8 accurately predicted the reactions that contributed to methane oxidation and growth under low oxygen but did not capture the relative contribution of its pMMO versus pXMO paralogs [ 12 ]. Thus, if the differential expression of paralogous genes is of interest, these details would need to be analyzed in separate empirical experiments.…”

“…At the same time, the model predicted the fraction of ATP generation from substrate-level phosphorylation to be roughly 71%, which provided quantitative insights into the mixed mode of metabolism via simultaneous respiration and fermentation [ 63 ]. Likewise, a GEM constructed for Methylomicrobium album BG8 predicted that this methanotroph excretes acetate under lower oxygen conditions through a mixed metabolic mode, in which pathways for respiration and fermentation are both active [ 12 ]. In the same study, the authors used their experimentally validated GEM to simulate the organism’s system-level metabolic reaction to different oxygen-to-methane ratios.…”