Serine is an essential component in organisms as a building block of biomolecules, a precursor of metabolites, an allosteric regulator of an enzyme, etc. This amino acid is thought to be a key metabolite in human diseases including cancers and infectious diseases. To understand the consequence of serine catabolism, we screened natural products to identify a fungal metabolite chaetoglobosin D (ChD) as a specific inhibitor of fission yeast cell growth when cultivated with serine as a sole nitrogen source. ChD targets actin, and actin mutant cells showed severe growth defect on serine medium. ROS accumulated in cells when cultivated in serine medium, while actin mutant cells showed increased sensitivity to oxidative stress. ROS production is a new aspect of serine metabolism, which might be involved in disease progression, and actin could be the drug target for curing serine-dependent symptoms.