Cofactor F430

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Cofactor F430
Coenzyme F430.svg
3D model (JSmol)
Molar mass 906.58014
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

F430 is the prosthetic group of the enzyme methyl coenzyme M reductase (MCR).[1] MCR catalyzes the release of methane in the final step of methanogenesis:

+ CoB–S–S–CoM

It is found only in methanogenic Archaea[2] and anaerobic methanotrophic Archaea. It occurs in relatively high concentrations in archaea that are thought to be involved in reverse methanogenesis. Organisms that promote this remarkable reaction contain 7% by weight nickel protein.[3]


The structure of F430 was deduced by X-ray crystallography and NMR spectroscopy.[4] Coenzyme F430 features the most reduced tetrapyrroles. In addition, it possesses two additional rings in comparison to the standard tetrapyrrole ring scaffold (rings A-D), with a γ-lactam ring E and a keto-containing carbocyclic ring F. It is the only natural tetrapyrrole containing nickel. Nickel is relatively infrequent in terms of metals in biology.


The biosynthesis begins with uroporphyrinogen III, the progenitor of all natural tetrapyrroles, including chlorophyll, vitamin B12, phycobilins, siroheme, heme, and heme d1. Uroporphyrinogen III is converted to sirohydrochlorin.[5] Insertion of nickel into this tetrapyrrole is catalysed by a class II chelatase (CfbA), generating nickel(II)-sirohydrochlorin.

An ATP-dependent amidase converts the a and c acetate side chains to acetamide, generating nickel(II)-sirohydrochlorin a,c-diamide. A two-component complex (CfbCD) carries out a 6-electron and 7-proton reduction of the ring system to generate 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, an ATP-dependent MurF-like ligase (found in peptidoglycan biosynthesis) form the final keto-containing carbocylic ring F, generating coenzyme F430.[6][7] As an amine source, this reaction uses either glutamine or free ammonia. The sequence of the two amidations is random.[7]


  1. ^ Stephen W., Ragdale (2014). "Chapter 6. Biochemistry of Methyl-Coenzyme M Reductase: The Nickel Metalloenzyme that Catalyzes the Final Step in Synthesis and the First Step in Anaerobic Oxidation of the Greenhouse Gas Methane". In Peter M.H. Kroneck and Martha E. Sosa Torres. The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment. Metal Ions in Life Sciences. 14. Springer. pp. 125–145. doi:10.1007/978-94-017-9269-1_6. ISBN 978-94-017-9268-4. PMID 25416393.
  2. ^ Thauer RK (1998). "Biochemistry of Methanogenesis: a Tribute to Marjory Stephenson". Microbiology. 144 (9): 2377–2406. doi:10.1099/00221287-144-9-2377. PMID 9782487.
  3. ^ Krüger M, Meyerdierks A, Glöckner FO, et al. (December 2003). "A conspicuous nickel protein in microbial mats that oxidize methane anaerobically". Nature. 426 (6968): 878–81. doi:10.1038/nature02207. PMID 14685246.
  4. ^ Färber G, Keller W, Kratky C, Jaun B, Pfaltz A, Spinner C, Kobelt A, Eschenmoser A (1991). "Coenzyme F430 from Methanogenic Bacteria : Complete Assignment of Configuration Based on an X-ray Analysis of 12,13-diepi-F430 Pentamethyl Ester and on NMR Spectroscopy". Helvetica Chimica Acta. 74 (4): 697–716. doi:10.1002/hlca.19910740404.
  5. ^ Mucha, Helmut; Keller, Eberhard; Weber, Hans; Lingens, Franz; Trösch, Walter (1985-10-07). "Sirohydrochlorin, a precursor of factor F430 biosynthesis in Methanobacterium thermoautotrophicum". FEBS Letters. 190 (1): 169–171. doi:10.1016/0014-5793(85)80451-8.
  6. ^ Zheng K, Ngo PD, Owens VL, Yang XP, Mansoorabadi SO, et al. (October 2016). "The biosynthetic pathway of coenzyme F430 in methanogenic and methanotrophic archaea". Science. 354 (6310): 339–342. doi:10.1126/science.aag2947. PMID 27846569.
  7. ^ a b Moore, Simon J.; Sowa, Sven T.; Schuchardt, Christopher; Deery, Evelyne; Lawrence, Andrew D.; Ramos, José Vazquez; Billig, Susan; Birkemeyer, Claudia; Chivers, Peter T. (2017-03-02). "Elucidation of the biosynthesis of the methane catalyst coenzyme F430". Nature. 543 (7643): 78–82. doi:10.1038/nature21427. ISSN 0028-0836. PMC 5337119. PMID 28225763.