Atranone-an underestimated secondary metabolite?

Abstract

Atranones are secondary metabolites produced by Stachybotrys chartarum, a mold frequently found in water-damaged indoor environments. In contrast to the well-characterized and highly toxic macrocyclic trichothecenes, atranones have received relatively limited scientific attention. Approximately 60% of S. chartarum isolates from indoor environments produce atranones, while 40% form macrocyclic trichothecenes. No strain has been shown to produce both, indicating that the biosynthetic pathways for these two mycotoxin classes are mutually exclusive. Atranones are dolabellane-like diterpenoids synthesized from geranylgeranyl pyrophosphate through multiple enzymatic steps encoded by a specific core gene cluster. While the genetic structure of this cluster has been elucidated, its regulatory mechanisms remain poorly understood. Notably, although atranone-producing S. chartarum strains have been isolated from indoor settings, no study has yet confirmed the actual production of atranones in indoor environments, leaving the question of real-world exposure unresolved. Experimental studies in cell cultures and animal models indicate that atranones possess pro-inflammatory and cytotoxic properties, including the induction of apoptosis and cell cycle arrest. Atranone Q has demonstrated antitumor activity against osteosarcoma cells in vitro, and more recently identified derivatives such as stachatranone and stachybatranone have shown preliminary cardioprotective effects under ischemic conditions. However, these pharmacological effects remain exploratory and require further validation in in vivo models. Major knowledge gaps concern the environmental triggers for atranone biosynthesis, their regulation, actual presence in built environments, and potential health risks. These areas represent key priorities for future research.