F₄₃₀ is the cofactor (sometimes called the coenzyme) of the enzyme

methyl coenzyme M reductase In enzymology, coenzyme-B sulfoethylthiotransferase, also known as methyl-coenzyme M reductase (MCR) or most systematically as 2-(methylthio)ethanesulfonate:N-(7-thioheptanoyl)-3-O-phosphothreonine S-(2-sulfoethyl)thiotransferase is an enzyme that ...

(MCR). MCR catalyzes the reaction that releases methane in the final step of

methanogenesis Methanogenesis or biomethanation is the formation of methane coupled to energy conservation by microbes known as methanogens. Organisms capable of producing methane for energy conservation have been identified only from the domain Archaea, a group ...

: : + HS–CoB → + CoB–S–S–CoM It is found only in

methanogen Methanogens are microorganisms that produce methane as a metabolic byproduct in hypoxic conditions. They are prokaryotic and belong to the domain Archaea. All known methanogens are members of the archaeal phylum Euryarchaeota. Methanogens are com ...

Archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...

and anaerobic methanotrophic Archaea. It occurs in relatively high concentrations in archaea that are involved in reverse methanogenesis: these can contain up to 7% by weight of the nickel protein.

Structure

The trivial name cofactor F₄₃₀ was assigned in 1978 based on the properties of a yellow sample extracted from '' Methanobacterium thermoautotrophicum'', which had a spectroscopic maximum at 430 nm. It was identified as the MCR cofactor in 1982 and the complete structure was deduced by X-ray crystallography and NMR spectroscopy. Coenzyme F₄₃₀ features a reduced porphyrin in a macrocyclic ring system called a corphin. In addition, it possesses two additional rings in comparison to the standard tetrapyrrole (rings A-D), having a γ-lactam ring E and a keto-containing carbocyclic ring F. It is the only natural tetrapyrrole containing nickel, an element rarely found in biological systems.

Biosynthesis

The biosynthesis builds from uroporphyrinogen III, the progenitor of all natural tetrapyrroles, including chlorophyll, vitamin B₁₂, phycobilins, siroheme, heme, and heme ''d''₁. It is converted to sirohydrochlorin via dihydrosirohydrochlorin. Insertion of nickel into this tetrapyrrole is catalysed in reaction by the same

chelatase In biochemistry, chelatases are enzymes that catalyze the insertion ("metalation") of naturally occurring tetrapyrroles. Many tetrapyrrole-based cofactors exist in nature including hemes, chlorophylls, and vitamin B12. These metallo cofactors are ...

, CbiX, which inserts cobalt in the biosynthesis of cobalamin, here giving nickel(II)-sirohydrochlorin. Biosynthesis of seco Cofactor F430

The ATP-dependent Ni-sirohydrochlorin a,c-diamide synthase (CfbE) then converts the ''a'' and ''c'' acetate side chains to acetamide in reactions , generating nickel(II)-sirohydrochlorin ''a'',''c''-diamide. The sequence of the two amidations is random. A two-component complex Ni-sirohydrochlorin a,c-diamide reductive cyclase (CfbCD) carries out a 6-electron and 7-proton reduction of the ring system in a reaction generating the 15,17³-''seco''-F₄₃₀-17³-acid (''seco''-F₄₃₀) intermediate. Reduction involves ATP hydrolysis and electrons are relayed through two 4Fe-4S centres. In the final step, the keto-containing carbocylic ring F is formed by an ATP-dependent enzyme Coenzyme F(430) synthetase (CfbB) in reaction , generating coenzyme F₄₃₀. This enzyme is a MurF-like ligase, as found in peptidoglycan biosynthesis.

References

{{Enzyme cofactors Tetrapyrroles Cofactors Nickel compounds