| [ Summary ] |
In prokaryotes, menaquinone (MK) is a lipid-soluble molecule which shuttles electrons between membranebound protein complexes in the electron transport chain. MK biosynthetic pathway was established through pioneering studies with E. coli, which derived from chorismate via o-succinylbenzoate. This was long accepted as the primary pathway. However, some years ago, there was a revision in the understanding of two successive biosynthetic steps, which lead to the conversion of isochorismate into 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate, were revised.
In contrast, Streptomyces coelicolor, whose genome sequencing has been completed, does not possess orthologues of the thus identified men genes, except for the two genes, menA and menG, which catalyse prenylation and methylation, respectively, although the strain produces MK. We therefore investigated this novel pathway. On the basis of bioinformatic screenings, gene knockouts, shotgun cloning with isolated mutants and in vitro studies with recombinant enzymes, we deduced the outline of the pathway (futalosine pathway). Moreover, we recently found that aminodeoxyfutalosine, which has adenine instead of hypoxanthine in futalosine, is directly converted into DHFL by an MqnB of Helicobacter pylori. Therefore, this step is potentially an attractive target for the development of specific anti-H. pylori drugs. In this review, details of the recent studies of both traditionally recognized and new pathways are presented. |