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Biosynthesis and its regulation

We have long-standing interests in primary metabolism particularly in the biosynthesis of pantothenate (vitamin B5) and de novo purine biosynthesis. We have also worked on aspects of thiamin biosynthesis, aromatic amino acid degradation and sirohaem biosynthesis.

Our current principal interests are in the characterisation of protein-protein interactions between enzymes in metabolic pathways and other cellular enzymes and we have recently reported the first biophysical characterisation of the interaction between ADC and the fifth enzyme in the pantothenate biosynthetic pathway, PanZ.

The pathway to pantothenate in the gamma-proteobacteria (see above) requires five enzymes: PanB, PanC, PanE (or IlvC), PanD and finally PanZ which is required for the activation of PanD. PanD and PanZ interact tightly to form a 1:1 complex as determined by ITC.

Publications in this area

The Structure of the PanD/PanZ Protein Complex Reveals Negative Feedback Regulation of Pantothenate Biosynthesis by Coenzyme A
Diana C.F. Monteiro, Vijay Patel, Christopher P. Bartlett, Shingo Nozaki, Thomas D. Grant, James A. Gowdy, Gary S. Thompson, Arnout P. Kalverda, Edward H. Snell, Hironori Niki, Arwen R. Pearson & Michael E. Webb Chem. Biol. (2015) 22 492-503

Pantothenate biosynthesis in higher plants Michael E Webb and Alison G Smith. Adv. Botan. Res. (2011), 58, 203-255

Riboswitches regulate thiamine biosynthesis in the model green algaChlamydomonas reinhardtii Martin T Croft, Michael Moulin, Michael E Webb and Alison G Smith Proc. Natl. Acad. Sci. U. S. A. (2007) 104 20770-20775

Biosynthesis of pantothenate Michael E. Webb, Alison G. Smith and Chris Abell Nat. Prod. Rep. (2004) 21 695-721