MethylH4MPT

MethylH4MPT, short for methyl-tetrahydromethanopterin, is a methylated derivative of tetrahydromethanopterin (H4MPT), a pterin-based cofactor found in many methanogenic archaea. It functions as a one-carbon carrier within the archaeal C1 metabolism that underpins methanogenesis, the biological production of methane.

In the methanogenesis pathway, methylH4MPT serves as the methyl donor in the transfer to coenzyme M (CoM). The enzyme methyl-H4MPT:CoM methyltransferase (Mtr) catalyzes the transfer of the methyl group from methylH4MPT to CoM, forming methyl-CoM and regenerating the oxidized H4MPT. The methyl-CoM is subsequently reduced to methane by methyl-coenzyme M reductase (MCR), a key terminal enzyme in methane formation, with coenzyme B participating in the final reductive step. This sequence links the one-carbon pool carried by H4MPT to the energy-conserving steps of methanogenesis.

Structurally, H4MPT provides a flexible scaffold for carrying various oxidation states of one-carbon units. MethylH4MPT represents a specific methylated state on this scaffold, and it is part of a dynamic cofactor cycle that regenerates H4MPT after methyl transfer. The methyl group on methylH4MPT originates from the surrounding C1 metabolic network and is ultimately converted into methane.

Distribution and significance: methylH4MPT is predominantly found in methanogenic archaea and is a hallmark of the archaeal methanogenesis pathway. It is not used in bacteria or eukaryotes. The methylH4MPT/Mtr step is a major control point in methane biosynthesis and a focus of study in microbial carbon cycling and energetics.