A Japanese research team from the Biotechnology Research Center in Toyama performed a bioinformatic analysis of whole genome sequences in order to find orthologues of the men genes in Escherichia coli. The men genes enable microorganisms to synthesise menaquinone (vitamin K2), an essential component of the electron-transfer pathway. In E. coli it is derived from chorismate by seven enzymes.

The genome analysis showed that some bacteria, e.g. Helicobacter pylori and Campylobacter jejuni, do not possess any orthologues of the men genes although they do synthesize menaquinone. Among those species were also pathogenic microorganisms. To find the alternative pathway, a bioinformatic screening was performed on a non-pathogenic strain of Streptomyces. Gene knockouts, shotgun cloning with isolated mutants and in vitro studies with recombinant enzymes were also used to determine the course of action required for producing menaquinone without the men genes.

Humans and commensal intestinal bacteria like the beneficial lactobacilli do not use the familiar pathway, which is why the alternative is an attractive target to use when developing new chemotherapeutics.

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Escherichia coli

Helicobacter pylori

Campylobacter jejuni

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