Production and purification of methionine gamma-lyase from Iranian soil mulds: investigation of physicochemical properties and anticancer effects

Abstract Cancer’s rising global incidence necessitates innovative therapies targeting the unique metabolic vulnerabilities of tumor cells. This study investigates microbial methionine gamma-lyase (MGL), an enzyme that depletes methionine, as a potential anticancer agent. Elevated methionine levels drive tumor progression by promoting S-adenosyl methionine (SAM) synthesis, leading to hypermethylation of tumor suppressor genes. By reducing methionine availability, MGL may inhibit SAM formation, preserving tumor suppressor function and hindering cancer growth. Three novel Iranian fungal strains—Penicillium flavigenum, Stagonosporopsis cucurbitacearum, and Penicillium allii—were identified as MGL producers through ITS sequencing. MGL was purified from P. flavigenum, and its biochemical properties, including stability, optimal pH, and temperature, were characterized, revealing high affinity for L-methionine and strong catalytic efficiency. Expression analysis of apoptotic genes (BCL-2 and caspase-3) demonstrated MGL’s role in enhancing apoptosis. In vitro assays confirmed its effectiveness against breast (MCF-7), liver (Hep G2), leukemia (MOLT-4), and glioblastoma (U87MG) cancer cell lines, with minimal toxicity to normal cells. This study underscores the therapeutic potential of fungal-derived MGL as a novel anticancer agent, highlighting its ability to modulate apoptotic pathways and providing a foundation for future clinical applications.