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Biological Sciences

Professor Chris Anthony BSc, PhD, DSc

Emeritus Professor

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Professor Chris Anthony is Emeritus Professor within Biological Sciences at the University of Southampton.

Career history

Emeritus Professor, University of Southampton, UK.
1993-1996: Head of Biochemistry Department, University of Southampton, UK.
Reader in Biochemistry, University of Southampton, UK.
Lecturer & Personal Chair in Biochemistry, University of Southampton, UK.
Postdoctoral Research Fellow, University of Sheffield, UK.

Academic qualifications

BSc Microbiology, University of Reading, UK.
PhD Microbial Biochemistry, University of Reading, UK.
DSc Microbial Biochemistry, University of Reading, UK.




Research interests

My main areas of research are more extensively described on my personal website.

The Biochemistry of Methylotrophs

Microbes that are able to grow on compounds with only one carbon atom [C1-compounds] such as methane, methanol, methylamine etc are called Methylotrophs. All the earlier work on these microbes is described in my book The Biochemistry of Methylotrophs. This is available in its entirety at Methylotrophs

My main interests are their carbon assimilation pathways and their energy transduction mechanisms. The first step in the oxidation of methanol is catalysed by the enzyme methanol dehydrogenase [MDH]. We first described this in 1964 and later showed it to be a new type of enzyme having a completely novel prosthetic group called PyrroloQuinoline Quinone [PQQ]; it was the first of a whole new family of enzymes called quinoproteins.

The PQQ-containing quinoproteins

These are the equivalent of flavoproteins that have the riboflavin derivatives FMN or FAD as their prosthetic groups. A major part of my work has been working out how energy [ATP] is obtained by linking the methanol dehydrogenase [MDH] in an electron transport chain to oxygen. After our discovery of PQQ [whose structure was later determined by others] it was found to be the prosthetic group of other bacterial enzymes such as glucose dehydrogenase [GDH] and we have also been involved in studies of this quinoprotein.

The structure and mechanism of the quinoprotein methanol dehydrogenase.
Our X-ray structure of methanol dehydrogenase was the first high resolution structure of a quinoprotein. It has an tetrameric structure. The α 2β 2-subunit (600 amino acids) is a superbarrel made up of eight radially-arranged β-sheets (the 'propeller fold'). PQQ, intimately bonded to a Ca2+ ion, is buried in the interior of the superbarrel. The floor of the active site chamber is formed by a tryptophan residue and the ceiling formed by a ring structure arising from a disulphide bridge between adjacent cysteine residues joined by a novel non-planar peptide bond. This is the only example of such a structure in an active enzyme; reduction inactivates (reversibly) the enzyme but its function is unknown. It has been proposed that a catalytic base (possibly Asp303) initiates the reaction by abstraction of a proton from the alcohol substrate. The Ca2+ ion is coordinated to The C-5 carbonyl oxygen of PQQ thus facilitating polarisation of the electrophilic C-5 for subsequent attack by an oxyanion or hydride. For more information and views of structure see MDH

The proposed role of PQQ as a vitamin

This topic is covered in detail, including a full illustrated lecture at PQQ

No mammalian PQQ-containing enzyme has been described. If such an enzyme does exist then it is very likely that PQQ will be a vitamin [analogous to riboflavin, needed in the diet for production of essential flavoproteins]. Although nutritional experiments have indicated some (unknown) metabolic or nutritional role for PQQ in mammals, it cannot seriously be accepted as a vitamin until an enzyme can be shown to require it as its cofactor. About one year ago Kasahara and Kato claim to have provided this evidence and announced ‘A new redox-cofactor vitamin for mammals' in Nature. This was greeted with enthusiasm by Reuters news agency “The first new vitamin for 55 years”, and its exploitation by Mitsubishi seems to be underway. However, the claim of Kasahara and Kato was based on sequence analysis of an enzyme, predicted to be involved in mouse lysine metabolism, using databases and search engines which inappropriately label beta propeller sequences as PQQ-binding sites. The ‘sites' wrongly identified by the databases do not represent PQQ-binding sites but represent the beta-sheets that form the ‘blades' of the ‘propeller fold' which happens to be a feature of all PQQ-dependent dehydrogenases, whose main structure is a superbarrel made up of either six or eight ‘propeller blades'. What the evidence actually suggests is that their (predicted) enzyme is an interesting novel protein having an eight-bladed beta propeller structure; but there is no evidence that it is a PQQ-dependent dehydrogenase. There is also no evidence that this protein has any relevance to lysine metabolism.

We argue that the conclusion that the mouse contains a PQQ-dependent dehydrogenase (and hence that PQQ is a vitamin) is an inappropriate conclusion from the evidence presented, and that the enthusiastic welcome with which this ‘new vitamin' was subsequently greeted was therefore misplaced. Our objections are published in Nature [Felton, L. M. & Anthony, C. Role of PQQ as a mammalian enzyme cofactor? Nature doi:10.1038/nature03322 (2005) ], together with further objections by Rucker and colleagues [Rucker, R., Storms, D., Sheets, A., Tchaparian, E. & Fascetti, A. Nature doi:10.1038/nature03323 (2005)] and a response by the original authors [ Takaoki Kasahara , T. & Kato, T. Nature doi:10.1038/nature03324(2005)].

The electron transport chain from methanol dehydrogenase involves two unusual c-type cytochromes; cytochrome cL is the initial electron acceptor and cytochrome cH mediates electron transfer to the oxidase. For the structures go to Cytochromes

Cytochrome cH : This small cytochrome mediates electron flow from cytochrome cLto the oxidase. Cytochrome cH is the electron donor to the oxidase in methylotrophic bacteria. Its amino acid sequence suggests that it is a typical Class I cytochrome c, but some features of the sequence indicated that its structure might be of special interest. The structure of oxidized cytochrome cH has been solved to 2.0 Å resolution by X-ray diffraction. It has the classical tertiary structure of the Class 1 cytochromes c but bears a closer gross resemblance to mitochondrial cytochrome c than to the bacterial cytochrome c2. The left-hand side of the haem cleft is unique; in particular, it is highly hydrophobic, the usual water is absent, and the “conserved” Tyr67 is replaced by tryptophan. A number of features of the structure demonstrate that the usual hydrogen bonding network involving water in the haem channel is not essential and that other mechanisms may exist for modulation of redox potentials in this cytochrome.

Cytochrome cL : The structure of cytochrome cL from Methylobacterium extorquens has been determined by X-ray crystallography to a resolution of 1.6 A ° . This unusually large, acidic cytochrome is the physiological electron acceptor for the quinoprotein methanol dehydrogenase in the periplasm of methylotrophic bacteria. Its amino acid sequence is completely different from that of other cytochromes but its X-ray structure reveals a core that is typical of class I cytochromes c, having a-helices folded into a compact structure enclosing the single haem c prosthetic group and leaving one edge of the haem exposed. The haem is bound through thioether bonds to Cys65 and Cys68, and the fifth ligand to the haem iron is provided by His69. Remarkably, the sixth ligand is provided by His112, and not by Met109, which had been shown to be the sixth ligand in solution.

Cytochrome cL is unusual in having a disulphide bridge that tethers the long C-terminal extension to the body of the structure. The crystal structure reveals that, close to the inner haem propionate, there is tightly bound calcium ion that is likely to be involved in stabilization of the redox potential, and that may be important in the flow of electrons from reduced pyrroloquinoline quinone in methanol dehydrogenase to the haem of cytochrome cL. As predicted, both haem propionates are exposed to solvent, accounting for the unusual influence of pH on the redox potential of this cytochrome.

Research group

Molecular and Cellular Biosciences

Anthony, C. (2011). How half a century of research was required to understand bacterial growth on C1 and C2 compounds; the story of the serine cycle and the ethylmalonyl-CoA pathway. Science Progress, 94, 109-137.

Anthony, C. (2008) A tribute to Howard Dalton and methane monooxygenase. Science Progress, 91, 401-415.

Paul Williams, Leighton Coates, Fiyaz Mohammed, Raj Gill Peter Erskine, Dominique Bourgeois, Steve P. Wood, Chris Anthony and Jonathan B. Cooper* (2006). The 1.6 A° X-ray Structure of the Unusual c-type Cytochrome, Cytochrome cL, from the Methylotrophic Bacterium Methylobacterium extorquens. J. Mol. Biol. 357, 151–162

P A Williams, L Coates, F Mohammed, R Gill, P T Erskine, A Coker, S P Wood, C Anthony, J B Cooper (2005) . The atomic resolution structure of methanol dehydrogenase from Methylobacterium extorquens. Acta Crystallogr D Biol Crystallogr. 61:75-9

Felton, L. M. & Anthony, C. (2005). Role of PQQ as a mammalian enzyme cofactor? Nature doi:10.1038/nature03322

DP Kelly, C Anthony, JC Murrell (2005) . Insights into the obligate methylotroph Methylococcus capsulatus. Trends in Microbiology 13, 195-198.

Anthony, C. (2004). The quinoprotein dehydrogenases for methanol and glucose. Archiv. Biochem. Biophys . 428 , 2-9.

Anthony, C. (2004) The Pyrroloquinoline Quinone (PQQ)-Containing Dehydrogenases. In Zannoni D. (ed): Respiration in Archaea and Bacteria. Vol. 1. Diversity of Prokaryotic Electron Transport Carriers, pp. 203-225. Kluwer Academic Publishers. Printed in The Netherlands.

Anthony, C. and Williams, P.W. (2003). The structure and function of methanol dehydrogenase. Biochim. Biophys. Acta 1467, 18-23

James, P.L. and Anthony, C. (2003). The metal ion in the active site of the membrane glucose dehydrogenase of Escherichia coli . Biochim. Biophys. Acta 1467, 200-205.

Toyama , H., Inagaki, H., Migita, T., Matsushita, K., Anthony, C. and Adachi, O. (2003).The role of the MxaD protein in the respiratory chain of Methylobacterium extorquens during growth on methanol. Biochim. Biophys. Acta 1467, 372-375.

Anthony, C., John, R.A, and Wilmot, C.M. (Eds) (2003). Special Issue: 3 rd International Symposium on Vitamin B 6 , PQQ, Carbonyl catalysis and Quinoproteins. Biochim. Biophys. Acta 1647, 1-408.

Afolabi, P.R. Mohammed, F., Amaratunga, K., Majekodunmi, O., Dales, S.L., Gill, R., Thompson, D., Cooper, J.B., Wood, S.P., Goodwin, P.M. and Anthony, C. (2001). Site-directed mutagenesis and X-ray crystallography of the PQQ-containing quinoprotein methanol dehydrogenase and its electron acceptor cytochrome c. Biochemistry 40, 9799-9809.

Anthony, C. (2001). Pyrroloquinoline quinone (PQQ) and quinoprotein enzymes. Antioxidants and Redox signalling 3, 757-774.

Anthony, C. (2000). Methanol dehydrogenase; a PQQ-containing quinoprotein dehydrogenase. In Enzyme-catalysed electron and radical transfers. Subcellular Biochemistry 35, 273-118.

Cozier, G.E., Salleh, R.A. & Anthony, C. (1999). Characterisation of the membrane glucose dehydrogenase from Escherichia coli and characterisation of a site directed mutant in which His262 has been changed to tyrosine. Biochem. J. 340, 639-647.

Anthony, C. & Ghosh, M. (1998). The structure and function of the PQQ-containing quinoprotein dehydrogenases. Progress in Biophysics and Molecular Biology 69, 1-21.

Anthony, C. (1998). Quinoprotein-catalysed reactions. In Comprehensive Biological Catalysis, Academic Press (Ed, M. Sinnott), 155-180.

Goodwin, P.M. & Anthony, C. (1998). The biochemistry, physiology and genetics of PQQ and PQQ-containing enzymes. Advances in Microbial Physiology 40, 1-80.

Read, J., Gill, R., Dales, S. D., Cooper, J.B., Wood, S.P. & Anthony, C. (1999). The molecular structure of an unusual cytochrome c 2 determined at 2.0 ? ; the cytochrome c H from Methylobacterium extorquens. Protein Science 8, 1232-1240

Toyama H., Anthony, C. & Lidstrom, M.E. (1998). Construction of insertion and deletion mxa mutants of Methylobacterium extorquens AM1 by electroporation. FEMS Microbiol. Letts. 166, 1-7.

Amaratunga, K., Goodwin, P.M., O'Connor, C.D. & Anthony, C. (1997). The methanol oxidation genes mxaFJGIR(S)ACKLD in Methylobacterium extorquens. FEMS Microbiol. Lett. 146, 31-38.

Anthony, C. (1996). Quinoprotein-catalysed reactions. Biochem.J. 320, 697-711.

Anthony, C. and Ghosh, M. (1996). The structure and function of PQQ-containing quinoproteins. Current Science ( India ) 72, 716-727.

Goodwin, M.G. & Anthony, C. (1996). Characterisation of a novel methanol dehydrogenase containing a Ba 2+ ion at the active site. Biochem. J. 318, 673-679.

Goodwin, M.G., Avezoux, A., Dales, S.L. & Anthony, C. (1996). Reconstitution of the quinoprotein methanol dehydrogenase from active Ca 2+ -free enzyme with Ca 2+ , Sr 2+ or Ba 2+ . Biochem. J. 319, 839-842.

Avezoux, A., Goodwin, M.G. & Anthony, C. (1995). The role of the novel disulphide ring in the active site of the quinoprotein methanol dehydrogenase from Methylobacterium extorquens. Biochemical Journal 307, 735-741.

Cozier, G.E., Giles, I.G. & Anthony, C. (1995). The structure of the quinoprotein alcohol dehydrogenase of Acetobacter aceti modelled on that of methanol dehydrogenase from Methylobacterium extorquens. Biochemical Journal 308, 375-379.

Dales, S.L. & Anthony, C. (1995). The interaction of methanol dehydrogenase and its cytochrome electron acceptor. Biochem. J. 312, 261-265.

Ghosh, M., Anthony, C., Harlos, K., Goodwin, M.G. & Blake, C.C.F. (1995). The refined structure of the quinoprotein methanol dehydrogenase from Methylobacterium extorquens at 1.94Å. Structure 3, 177-187.

Professor Chris Anthony
Biological Sciences Faculty of Natural & Environmental Sciences Life Sciences Building 85 University of Southampton Highfield Campus Southampton SO17 1BJ

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