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An alternative menaquinone biosynthetic pathway operating in microorganisms
Authors:Hiratsuka Tomoshige  Furihata Kazuo  Ishikawa Jun  Yamashita Haruyuki  Itoh Nobuya  Seto Haruo  Dairi Tohru
Institution:Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan.
Abstract:In microorganisms, menaquinone is an obligatory component of the electron-transfer pathway. It is derived from chorismate by seven enzymes in Escherichia coli. However, a bioinformatic analysis of whole genome sequences has suggested that some microorganisms, including pathogenic species such as Helicobacter pylori and Campylobacter jejuni, do not have orthologs of the men genes, even though they synthesize menaquinone. We deduced the outline of this alternative pathway in a nonpathogenic strain of Streptomyces by bioinformatic screening, gene knockouts, shotgun cloning with isolated mutants, and in vitro studies with recombinant enzymes. As humans and commensal intestinal bacteria, including lactobacilli, lack this pathway, it represents an attractive target for the development of chemotherapeutics.
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