Bacterial Biosynthesis of Menaquinones

Examination of some of the features of the biosynthesis of phylloquinones such as (9) in higher plants and of menaquinones (10) in bacteria has shown that the pol5qjrenyl chains and nuclear C methyl groups arise imexceptionally from (R)-mevalonic acid (11) and L-methionine respectively The aspect of biosynthesis which has commanded most attention is the building of the naphthoquinone nucleus from (—)-shikimic acid and almost all of the critical and pertinent observations upon this intriguing problem have been made in relation to menaquinones from bacterial sources. 

Campbell, I.M., Robins, D.J., Kelsey, M., and Bentley, R., Biosynthesis of bacterial menaquinones... 

Snyder, C.D. and Rapoport, H., Biosynthesis of bacterial menaquinones. Origin of quinone oxygens, Biochemistry, 9, 2033,1970. 

Menaquinone. The incorporation of [2- C]mevalonate and [2- C]-2-methyl-l,4-naphthoquinone into MK-4, normally considered a bacterial quinone, has been demonstrated in marine invertebrates such as crabs and starfish." Incorporation into 2,3-epoxy-MK-4 (163) was also observed. Cell-free extracts have been prepared from Escherichia coli which catalyse the conversion of o-succinylbenzoic acid (164) into l,4-dihydroxy-2-naphthoic acid (165) and menaquinones. In the presence of farnesyl pyrophosphate the major menaquinone produced was MK-3. Genetic studies with mutants of E. coli K12 that require (164) offer support for the generally accepted pathway for MK biosynthesis via (164) and (165)." The enzyme system that catalyses the attachment of the polyprenyl side-chain to 1,4-dihydroxy-2-naphthoic acid to form demethylmenaquinone-9 (166) has been isolated from E. colU ... 

Baldwin, Snyder and Rapoport in an important paper have directed attention at the symmetry (or otherwise) of the as yet unidentified naphthalenic intermediate in bacterial menaquinone biosynthesis. 7-[ C]-Shikimic acid, prepared by the procedure of Grewe and Vangermain from 3,4,5-triacetoxycyclohexanone, was incorporated (0.25 per cent) into 9-dihydromenaquinone (1) in Mycobacterium phlei. Degradation gave C-1 and C-4 of the original... 

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