Cofactor F430

Not to be confused with Coenzyme F420.

F₄₃₀ is the cofactor (sometimes called the coenzyme) of the enzyme methyl coenzyme M reductase (MCR).^[1][2] MCR catalyzes the reaction EC 2.8.4.1 that releases methane in the final step of methanogenesis:

CH
₃–S–CoM + HS–CoB → CH
₄ + CoB–S–S–CoM

Structure of coenzyme M (HS-CoM)

Structure of coenzyme B (HS-CoB)

Cofactor F430

Identifiers
CAS Number	73145-13-8 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:28265 Y
ChemSpider	21864910 Y
PubChem CID	5460020
InChI InChI=1S/C42H52N6O13.Ni/c1-40(16-30(43)50)22(5-9-33(54)55)27-15-42-41(2,17-31(51)48-42)23(6-10-34(56)57)26(47-42)13-24-20(11-35(58)59)19(4-8-32(52)53)39(45-24)37-28(49)7-3-18-21(12-36(60)61)25(46-38(18)37)14-29(40)44-27;/h13,18-23,25,27H,3-12,14-17H2,1-2H3,(H9,43,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61);/p-1/t18-,19-,20-,21-,22+,23+,25+,27-,40-,41-,42-;/m0./s1 Key: QFGKGCZCUVIENT-SXMZNAGASA-M
SMILES CC12CC(=O)NC13CC4C(C(C(=N4)CC5C(C6CCC(=O)C(=C7C(C(C(=CC(=N3)C2CCC(=O)O)[N-]7)CC(=O)O)CCC(=O)O)C6=N5)CC(=O)O)(C)CC(=O)N)CCC(=O)O.[Ni]
Properties
Chemical formula	C 42H 51N 6NiO− 13
Molar mass	906.58014
Appearance	Yellow solid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

It is found only in methanogenic Archaea^[3] 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.^[4]

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.^[5] It was identified as the MCR cofactor in 1982^[6] and the complete structure was deduced by X-ray crystallography and NMR spectroscopy.^[7] Coenzyme F₄₃₀ features a reduced porphyrin in a macrocyclic ring system called a corphin.^[8] 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. F₄₃₀ and its biosynthetic precursors represent the only known biologically occurring tetrapyrroles containing nickel, an element rarely found in life.^[9]

Biosynthesis

uroporphyrinogen III

dihydrosirohydrochlorin

sirohydrochlorin

The biosynthesis builds from uroporphyrinogen III, the progenitor of all natural tetrapyrroles, including chlorophyll, vitamin B₁₂, phycobilins, siroheme, heme, and heme d₁. It is converted to sirohydrochlorin via dihydrosirohydrochlorin.^[10] Insertion of nickel into this tetrapyrrole is catalysed in reaction EC 4.99.1.11 by the same chelatase, CbiX, which inserts cobalt in the biosynthesis of cobalamin, here giving nickel(II)-sirohydrochlorin.^[11]

Nickel(II)-sirohydrochlorin a,c-diamide is converted to seco-F430. It is traditional to depict only one of four Ni-N bonds.

The ATP-dependent Ni-sirohydrochlorin a,c-diamide synthase (CfbE) then converts the a and c acetate side chains to acetamide in reactions EC 6.3.5.12, generating nickel(II)-sirohydrochlorin a,c-diamide. The sequence of the two amidations is random.^[11] 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 EC 6.3.3.7 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 EC 6.4.1.9, generating coenzyme F₄₃₀.^[11][12][13] This enzyme is a MurF-like ligase, as found in peptidoglycan biosynthesis.

See also

• Abelsonite, a similarly nickel-containing geoporphyrin.