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Science 19 September 2008:
Vol. 321. no. 5896, pp. 1670 - 1673
DOI: 10.1126/science.1160446
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Reports

An Alternative Menaquinone Biosynthetic Pathway Operating in Microorganisms

Tomoshige Hiratsuka,1 Kazuo Furihata,2 Jun Ishikawa,3 Haruyuki Yamashita,4 Nobuya Itoh,1 Haruo Seto,5 Tohru Dairi1*

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.

1 Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan.
2 Division of Agriculture and Agricultural Life Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657 Japan.
3 Department of Bioactive Molecules, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
4 Advanced Materials Research and Development Laboratory, ADEKA Corporation, Arakawa-ku, Tokyo 116-8553, Japan.
5 Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502, Japan.

* To whom correspondence should be addressed. E-mail: dairi{at}pu-toyama.ac.jp

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