Beyond methanogenesis: Methanosarcina mazei in biotechnology and biomedical research

Abstract

Methanosarcina mazei is a metabolically versatile methanogenic archaeon that extends far beyond its classical role in methane production. Recent advances in genomics, proteomics, and systems biology have revealed a rich repertoire of unique genetic, enzymatic, and regulatory elements that make M. mazei a powerful chassis for biotechnological and biomedical applications. With a genome of ~ 4.1 Mbp and exceptional substrate flexibility, including acetate, methanol, methylamines, and H₂/CO₂, M. mazei demonstrates superior tolerance to salinity, ammonia, and organic acids, enabling its dominance in stressed anaerobic ecosystems. Emerging genetic engineering tools, including CRISPR-Cas systems, inducible promoters, and codon expansion via pyrrolysyl-tRNA synthetases, have opened new avenues for metabolic engineering, enzyme design, and synthetic biology. Notably, M. mazei supports sustainable bioplastic production, heavy metal bioremediation, and degradation of toxic pollutants under anoxic conditions. In biomedicine, its orthogonal translation system enables the precise incorporation of non-canonical amino acids, supporting applications in protein labeling, prodrug design and DNA repair. Furthermore, their involvement in the human microbiome, particularly in gut disorders and colorectal cancer, has sparked interest in their diagnostic and therapeutic potentials. This review summarizes the current knowledge of its unique biological features, engineered toolkits, and translational applications, establishing it as a next-generation model organism for systems biotechnology and archaeal synthetic biology.

Keywords

Methanosarcina mazei / Synthetic biology / Pyrrolysine / Bioplastics / Genetic engineering / Human diseases

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