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

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

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. 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 c ...

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 Archaeba ...

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 Spectroscopy is the field of study that measures and interprets the electromagnetic spectra that result from the interaction between electromagnetic radiation and matter as a function of the wavelength or frequency of the radiation. Matter wa ...

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 determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...

and

NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fi ...

. Coenzyme F₄₃₀ features a reduced

porphyrin Porphyrins ( ) are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). The parent of porphyrin is porphine, a rare chemical com ...

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 car ...

(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 with 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 slow t ...

, 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 Acetamide (systematic name: ethanamide) is an organic compound with the formula CH3CONH2. It is the simplest amide derived from 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 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 Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...

biosynthesis.

References

{{Enzyme cofactors Tetrapyrroles Cofactors Nickel compounds