Methanosarcina mazei is a metabolically versatile methanogenic archaeon that extends far beyond its classical role in meth-ane production.Recent advances in genomics,proteomics,and systems biology have revealed a rich...Methanosarcina mazei is a metabolically versatile methanogenic archaeon that extends far beyond its classical role in meth-ane 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 H_(2)/CO_(2),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 promot-ers,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.展开更多
基金the Science and Engineering Research Board,Ministry of Science and Technology,Government of India(EEQ/2020/000095)RUSA 2.0:Biological Science,Government of India(12/BDU/RUSA/TRP/BS),for their financial support。
文摘Methanosarcina mazei is a metabolically versatile methanogenic archaeon that extends far beyond its classical role in meth-ane 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 H_(2)/CO_(2),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 promot-ers,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.