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DNA Research Advance Access published online on May 16, 2008
DNA Research, doi:10.1093/dnares/dsn009
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© The Author 2008. Kazusa DNA Research Institute
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Comparative Genome Analysis of Lactobacillus reuteri and Lactobacillus fermentum Reveal a Genomic Island for Reuterin and Cobalamin Production

Hidetoshi Morita1,*, Hidehiro Toh2,3, Shinji Fukuda4,5, Hiroshi Horikawa1, Kenshiro Oshima3, Takehito Suzuki1, Masaru Murakami1, Shin Hisamatsu6, Yukio Kato1, Tatsuya Takizawa1, Hideo Fukuoka1, Tetsuhiko Yoshimura7, Kikuji Itoh8, Daniel J. O'Sullivan9, Larry L. McKay9, Hiroshi Ohno4,5, Jun Kikuchi5,10,11, Toshio Masaoka1 and Masahira Hattori2,12

1 School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501, Japan
2 RIKEN Genomic Sciences Center, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan
3 Kitasato Institute for Life Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan
4 RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan
5 International Graduate School of Arts and Sciences, Yokohama City University, 1-7-29 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan
6 College of Environmental Health, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501, Japan
7 Yamagata Promotional Organization for Industrial Technology, 2-2-1 Matsuei, Yamagata 990-2473, Japan
8 Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan
9 Department of Food Science and Nutrition, University of Minnesota, 1334 Eckles Avenue, St. Paul 55108, USA
10 RIKEN Plant Science Center, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan
11 Graduate School of Bioagriculture Sciences, Nagoya University, 1 Furo, Chikusa, Nagoya, Aichi 464-8601, Japan
12 Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan

Received 12 March 2008 ; accepted 10 April 2008.

Lactobacillus reuteri is a heterofermentative lactic acid bacterium that naturally inhabits the gut of humans and other animals. The probiotic effects of L. reuteri have been proposed to be largely associated with the production of the broad-spectrum antimicrobial compound reuterin during anaerobic metabolism of glycerol. We determined the complete genome sequences of the reuterin-producing L. reuteri JCM 1112T and its closely related species Lactobacillus fermentum IFO 3956. Both are in the same phylogenetic group within the genus Lactobacillus. Comparative genome analysis revealed that L. reuteri JCM 1112T has a unique cluster of 58 genes for the biosynthesis of reuterin and cobalamin (vitamin B12). The 58-gene cluster has a lower GC content and is apparently inserted into the conserved region, suggesting that the cluster represents a genomic island acquired from an anomalous source. Two-dimensional nuclear magnetic resonance (2D-NMR) with 13C3-glycerol demonstrated that L. reuteri JCM 1112T could convert glycerol to reuterin in vivo, substantiating the potential of L. reuteri JCM 1112T to produce reuterin in the intestine. Given that glycerol is shown to be naturally present in feces, the acquired ability to produce reuterin and cobalamin is an adaptive evolutionary response that likely contributes to the probiotic properties of L. reuteri.

Key words: Lactobacillus reuteri; Lactobacillus fermentum; reuterin; cobalamin; genome

* To whom correspondence should be addressed. Tel./fax: + 81 42-850-2450. E-mail: morita{at}azabu-u.ac.jp

Edited by: Katsumi Isono


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