In the relentless quest to combat cancer, one of the most formidable health challenges of our time, researchers are increasingly turning to the unique biochemical vulnerabilities of tumor cells. A groundbreaking study published in BMC Cancer unveils the promising potential of methionine gamma-lyase (MGL), an enzyme sourced from Iranian soil fungi, as a novel anticancer agent. This enzyme specifically targets methionine metabolism, a critical pathway exploited by cancer cells to fuel their unrestrained growth and proliferation.
Methionine, an essential amino acid, plays a pivotal role in cellular metabolism, particularly as a precursor for S-adenosyl methionine (SAM). SAM acts as a universal methyl donor, underpinning vital methylation processes that regulate gene expression. Aberrant methionine metabolism has been implicated in tumorigenesis through the hypermethylation of tumor suppressor genes, effectively silencing these natural brakes on cancer progression. By depleting methionine, MGL disrupts this chain, potentially restoring normal cellular regulation and triggering cancer cell death.
The study’s innovative approach began with the isolation of three novel fungal strains from Iranian soil – Penicillium flavigenum, Stagonosporopsis cucurbitacearum, and Penicillium allii. Using internal transcribed spacer (ITS) sequencing for precise taxonomic identification, the team established these soil molds as natural producers of MGL. Subsequently, the enzyme was purified from P. flavigenum, enabling detailed biochemical characterization not previously reported in the literature with such fungal sources.
Characterization revealed that the purified MGL possesses remarkable catalytic efficiency and substrate specificity, with a pronounced affinity for L-methionine. The enzyme demonstrated optimal activity at specific pH and temperature ranges, underscoring its stability and robustness under physiological conditions. Such physicochemical properties are critical for any therapeutic enzyme’s viability, suggesting that fungal-derived MGL can withstand the human body’s complex and variable microenvironment.
Beyond enzymatic activity, the research delved into the molecular underpinnings of MGL’s anticancer effects by analyzing the expression levels of key apoptotic regulators, including BCL-2, an anti-apoptotic protein, and caspase-3, a central executor of programmed cell death. Treatment with MGL resulted in downregulation of BCL-2 and concomitant activation of caspase-3, indicating that depletion of methionine not only stymies tumor metabolism but also actively engages apoptotic pathways to induce cancer cell demise.
The enzyme’s efficacy was rigorously tested in vitro against an array of human cancer cell lines representing diverse tissue origins: breast adenocarcinoma (MCF-7), hepatocellular carcinoma (Hep G2), acute lymphoblastic leukemia (MOLT-4), and glioblastoma multiforme (U87MG). In all cases, MGL treatment significantly inhibited cell proliferation while sparing normal, non-cancerous cells, highlighting its selective cytotoxicity—an essential feature for minimizing adverse effects in clinical settings.
These promising results mark a significant advance in oncoenzyme therapy, where metabolic enzymes are harnessed as precise molecular tools to counteract cancer’s metabolic aberrations. Methionine metabolism has long been recognized as a critical vulnerability in cancer, yet previous therapeutic attempts have been hindered by lack of specificity or insufficient enzymatic stability. The fungal-derived MGL characterized here provides a compelling alternative, blending potent methionine depletion capabilities with biochemical resilience.
Moreover, the choice of soil fungi as a source for MGL enriches the enzyme’s appeal. Soil microorganisms have evolved diverse metabolic pathways to survive in competitive environments, often producing enzymes with unique catalytic properties. Harvesting such naturally optimized enzymes may accelerate the development of effective, biologically compatible cancer therapeutics and reduce reliance on synthetic analogs, which can introduce risks of immunogenicity and off-target effects.
The study also opens exciting avenues for combining MGL therapy with existing cancer treatments. By inducing apoptosis via methionine deprivation, MGL may sensitize tumor cells to chemotherapeutic agents or radiation, thereby enhancing overall treatment efficacy while potentially allowing dose reductions that diminish toxicity. Future research will be needed to explore these combinatorial strategies in preclinical and clinical trials.
Notably, the comprehensive physicochemical profiling performed in this work sets a rigorous standard for enzyme-based drug development. Stability assays, kinetic measurements, and expression analysis collectively provide a blueprint for optimizing production, formulation, and delivery methods tailored to maintain enzyme activity throughout therapeutic protocols.
The selectivity demonstrated by MGL against cancer cells compared to normal cell lines holds promise for improved safety profiles. Conventional chemotherapies often suffer from dose-limiting side effects due to insufficient discrimination between healthy and malignant cells. MGL’s targeted mechanism of action, rooted in methionine metabolism dependence—a hallmark of many cancers—positions it as a potentially superior anticancer agent with fewer collateral damages.
In a broader context, this research exemplifies the burgeoning field of microbial enzymology applied to medicine, wherein natural enzymes are repurposed as precision therapeutics. It underscores the value of bioprospecting in diverse ecological niches, such as Iranian soils, as a strategy to discover novel bioactive molecules with transformative clinical implications.
The findings also emphasize the intricate link between cellular metabolism and epigenetics in cancer. By modulating SAM synthesis, MGL indirectly influences methylation patterns that govern tumor suppressor gene activity. This intersection of metabolic and epigenetic therapy represents a cutting-edge frontier in cancer biology, promising more refined and multifaceted interventions.
While encouraging, the translation of MGL therapy from bench to bedside will require overcoming hurdles such as enzyme delivery efficiency, stability within the human systemic circulation, immunogenicity mitigation, and scalable production. Nevertheless, the insights gained here pave the way for innovative biopharmaceutical engineering approaches to surmount these challenges.
In conclusion, the exploration of fungal-derived methionine gamma-lyase from Iranian soil molds provides a compelling new weapon in the fight against cancer. The enzyme’s dual role in depleting a crucial amino acid and activating apoptotic cascades illustrates the power of leveraging metabolic vulnerabilities. This study not only enriches our scientific understanding of MGL’s biochemical and anticancer properties but also charts a promising path toward effective, enzyme-based cancer therapeutics that may revolutionize future treatments.
Subject of Research: Methionine gamma-lyase production and purification from Iranian soil fungi; investigation of enzyme physicochemical properties and evaluation of anticancer effects through apoptosis modulation.
Article Title: Production and purification of methionine gamma-lyase from Iranian soil mulds: investigation of physicochemical properties and anticancer effects
Article References: Nasirian, M., Arab-SadeghAbadi, A., Mobini-Dehkordi, M. et al. Production and purification of methionine gamma-lyase from Iranian soil mulds: investigation of physicochemical properties and anticancer effects. BMC Cancer 25, 1339 (2025). https://doi.org/10.1186/s12885-025-14754-0
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14754-0
Keywords: Methionine gamma-lyase, fungal enzymes, cancer metabolism, methionine depletion, apoptosis, tumor suppressor gene methylation, oncoenzyme therapy, fungal bioprospecting, enzyme purification, anticancer biotherapeutics
