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

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

methyl coenzyme M reductase (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. It is the fourth and final stage of anaerobic digestion. Organisms capable of producing methane for energy conservation h ...

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

methanogen Methanogens are anaerobic archaea that produce methane as a byproduct of their energy metabolism, i.e., catabolism. Methane production, or methanogenesis, is the only biochemical pathway for Adenosine triphosphate, ATP generation in methanogens. A ...

Archaea Archaea ( ) is a Domain (biology), domain of organisms. Traditionally, Archaea only included its Prokaryote, prokaryotic members, but this has since been found to be paraphyletic, as eukaryotes are known to have evolved from archaea. Even thou ...

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 In chemistry, a trivial name is a non-systematic name for a chemical substance. That is, the name is not recognized according to the rules of any formal system of chemical nomenclature such as IUPAC inorganic or IUPAC organic nomenclature. A ...

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 X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...

and

NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic f ...

. Coenzyme F₄₃₀ features a reduced

porphyrin Porphyrins ( ) are heterocyclic, macrocyclic, organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (). In vertebrates, an essential member of the porphyrin group is heme, w ...

in a

macrocyclic Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry. ...

ring system called a corphin. In addition, it possesses two additional rings in comparison to the standard

tetrapyrrole Tetrapyrroles are a class of chemical compounds that contain four pyrrole or pyrrole-like rings. The pyrrole/pyrrole derivatives are linked by ( or units), in either a linear or a cyclic fashion. Pyrroles are a five-atom ring with four carbon ...

(rings A-D), having a γ-lactam ring E and a keto-containing carbocyclic ring F. It is the only natural tetrapyrrole containing

nickel Nickel is a chemical element; it has symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive, but large pieces are slo ...

, an element rarely found in biological systems.

Biosynthesis

The biosynthesis builds from

uroporphyrinogen III Uroporphyrinogen III is a tetrapyrrole, the first macrocycle, macrocyclic intermediate in the biosynthesis of heme, chlorophyll, vitamin B12, and siroheme. It is a colorless compound, like other porphyrinogens. Structure The molecular structure of ...

, 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, CbiX, which inserts cobalt in the biosynthesis of cobalamin, here giving nickel(II)-sirohydrochlorin. The ATP-dependent Ni-sirohydrochlorin a,c-diamide synthase (CfbE) then converts the ''a'' and ''c'' acetate side chains to

acetamide Acetamide (systematic name: ethanamide) is an organic compound with the formula CH3CONH2. It is an amide derived from ammonia and acetic acid. It finds some use as a plasticizer and as an industrial solvent. The related compound ''N'',''N''-dime ...

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 carbocyclic 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 Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating ...

biosynthesis.

References

{{Enzyme cofactors Tetrapyrroles Cofactors Nickel compounds