Before revision:  However, it requires solving a nonconvex optimization problem and its scalability to genome-scale modelshas not been demonstrated.
After revision:  However, it leads to nonconvex optimization problems, and existing tools cannot scale to realistically large metabolic models. Thus, constraint estimation is still used sparingly despite its benefits for modeling cell metabolism, which is important for developing novel antimicrobials against pathogens, discovering cancer drug targets, and producing value-added chemicals.