R. Meganathan

Menaquinone/Ubiquinone Biosynthesis and Enzymology

The naphthoquinones, menaquinone (Vitamin-K2), demethylmenaquinone, and phylloquinone (Vitamin K1) as well as the benzoquinone, ubiquinone (Coenzyme Q) are derived from the shikimate pathway which has been described as a ‘metabolic tree with many branches’. Although menaquinone (MK) and demethylmenaquinone (DMK) are present in bacteria, phylloquinone (K) occurs in plants, algae, and cyanobacteria. The MK and K differ from each other in that the prenyl side chain of the former is replaced by a phytyl side chain in the latter. In prokaryotes, there are two different pathways for the biosynthesis of MK. Both pathways are branches of the shikimate pathway that diverges at chorismate and converges at DMK. Among the MK-producing bacteria, the vast majority so far examined biosynthesize the quinone by the o-succinylbenzoate (OSB) pathway, whereas a small group of organisms was shown to produce MK by the non-o-succinylbenzoate (non-OSB) pathway or futalosine pathway. The oxygenic photosynthetic organisms synthesize K exclusively by the OSB pathway. However, in plants four of the MK biosynthetic genes menF, menD, menC, and menH are fused into a single gene called PHYLLO. The quinone nucleus of Q is derived from chorismate through 4-hydroxybenzoate (4-HB). However, depending on the organism, the 4-HB can be synthesized by three different routes. In this chapter, the biosynthesis of the naphthoquinone ring of MK and K by the OSB or non-OSB pathways as well as the benzoquinone ring of Q is presented. A comparative analysis of Q biosynthesis between Escherichia coli (a prokaryote) and Saccharomyces cerevisiae (a eukaryote) is provided. The various enzymatic reactions involved in the OSB pathway of MK biosynthesis and that of Q are presented from a mechanistic perspective.