Malformin A1

Malformin A1 is a cyclic pentapeptide originally isolated from Aspergillus niger and characterized as a phytotoxic fungal metabolite with a cyclo-D-Cys-D-Cys-L-amino acid-D-amino acid-L-amino acid core structure. It contains an internal disulfide bridge and exhibits diverse bioactivities. In cancer models, MA1 induces potent cytotoxicity through mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and activation of caspase-dependent apoptosis. It also stimulates p38 MAPK signaling and AMPK/mTOR-mediated autophagy, contributing to combined apoptotic, necrotic, and autophagic cell death. MA1 sensitizes cisplatin-resistant ovarian cancer cells and suppresses invasion and migration in colorectal cancer models. Additionally, it shows antiviral activity against Tobacco mosaic virus (TMV). These data position MA1 as a multifunctional fungal peptide affecting mitochondrial integrity and stress signaling pathways.