Constraint-based metabolic modeling reveals metabolic properties underpinning the unprecedented growth of Chlorella...

Comparative molecular and physiological analyses of organisms from one taxonomic group grown under similar conditions offer a strategy to identify gene targets for trait improvement. While this strategy can also be performed in silico using genome-scale metabolic models for the compared organisms, we continue to lack solutions for the de novo generation of such models, particularly for eukaryotes. To facilitate model-driven identification of gene targets for growth improvement in green algae, here we present a semiautomated platform for de novo generation of genome-scale algal metabolic models. We deployed this platform to reconstruct an enzyme-constrained, genome-scale metabolic model of Chlorella ohadii, the fastest growing green alga reported to date, and validated the growth predictions in experiments under three growth conditions. We also proposed a computational strategy to identify targets for growth improvement based on flux analyses. Extensive flux-based comparative analyses using all existing models of green algae resulted in the identification of potential targets for growth improvement not only in standard but also in extreme light conditions, where C. ohadii still exhibits exceptional growth. Our findings indicate that the developed platform provides the basis for the generation of pan-genome-scale metabolic models of algae.