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Papers In Press, published online ahead of print January 1, 2008
J. Lipid Res., doi:10.1194/jlr.M700377-JLR200

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Journal of Lipid Research, Vol. 49, 183-191, January 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

The repertoire of desaturases and elongases reveals fatty acid variations in 56 eukaryotic genomes

Kosuke Hashimoto^*, Akiyasu C. Yoshizawa^*, Shujiro Okuda^*, Keiichi Kuma, Susumu Goto^* and Minoru Kanehisa^1,*,

^* Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
National Institute of Informatics, Chiyoda-ku, Tokyo 101-8430, Japan
Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of two tables and eight figures.

Published, JLR Papers in Press, October 7, 2007.

¹ To whom correspondence should be addressed. e-mail: kanehisa{at}kuicr.kyoto-u.ac.jp

The repertoire of biosynthetic enzymes found in an organism is an important clue for elucidating the chemical structural variations of various compounds. In the case of fatty acids, it is essential to examine key enzymes that are desaturases and elongases, whose combination determine the range of fatty acid structures. We systematically investigated 56 eukaryotic genomes to obtain 275 desaturase and 265 elongase homologs. Phylogenetic and motif analysis indicated that the desaturases consisted of four functionally distinct subfamilies and the elongases consisted of two subfamilies. From the combination of the subfamilies, we then predicted the ability to synthesize six types of fatty acids. Consequently, we found that the ranges of synthesizable fatty acids were often different even between closely related organisms. The reason is that, as well as diverging into subfamilies, the enzymes have functionally diverged within the individual subfamilies. Finally, we discuss how the adaptation to individual environments and the ability to synthesize specific metabolites provides some explanation for the diversity of enzyme functions. This study provides an example of a potent strategy to bridge the gap from genomic knowledge to chemical knowledge.

Supplementary key words genome • bioinformatics • lipid • histidine box • motif analysis • phylogenetic analysis • evolution

Abbreviations: HMM, hidden Markov model; KEGG, Kyoto Encyclopedia of Genes and Genomes; SCD, stearoyl-coenzyme A desaturase

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