Published online 28 April 2009 Nucleic Acids Research, 2009, Vol. 37, Web Server issue W129–W134 doi:10.1093/nar/gkp264 FMM: a web server for metabolic pathway reconstruction and comparative analysis Chih-Hung Chou1, Wen-Chi Chang2,3, Chih-Min Chiu1, Chih-Chang Huang2 and Hsien-Da Huang2,3,* 1Institute of Molecular Medicine and Bioengineering, 2Institute of Bioinformatics and Systems Biology and 3Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu 300, Taiwan, Republic of China Received February 18, 2009; Revised April 6, 2009; Accepted April 8, 2009 ABSTRACT Synthetic Biology, a multidisciplinary field, is growing rapidly. Improving the understanding of biological systems through mimicry and producing bio-orthogonal systems with new functions are two complementary pursuits in this field. A web server called FMM (From Metabolite to Metabolite) was developed for this purpose. FMM can reconstruct metabolic pathways form one metabolite to another metabolite among different species, based mainly on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and other integrated biological databases. Novel presentation for connecting differ- ent KEGG maps is newly provided. Both local and global graphical views of the metabolic pathways are designed. FMM has many applications in Synthetic Biology and Metabolic Engineering. For example, the reconstruction of metabolic pathways to produce valuable metabolites or secondary meta- bolites in bacteria or yeast is a promising strategy for drug production. FMM provides a highly effective way to elucidate the genes from which species should be cloned into those microorganisms based on FMM pathway comparative analysis. Consequently, FMM is an effective tool for applica- tions in synthetic biology to produce both drugs and biofuels. This novel and innovative resource is now freely available at http://FMM.mbc.nctu.edu.tw/. INTRODUCTION Synthetic Biology, a rapidly growing multidisciplinary ﬁeld, has two complementary goals- further elucidating biological systems through mimicry and producing bio- orthogonal systems with new functions (1). Microbes are well established as eﬀective hosts for the biosynthesis of bio-molecules; consequently, engineered microbial biolog- ical systems represent critical frontier in synthetic biology (2). Engineered microorganisms are employed in numer- ous applications, including food additives, pharmaceuti- cals, fuels, animal feed supplements, cosmetics and polymer materials (3,4). For example, Corynebacterium glutamicum and Escherichia coli are used to produce lysine, methionine, valine and threonine (3,5–8) which are essential intermediate precursors for antibiotics (9) and biofuels (10). These beneﬁts have motivated scientists to design and construct new biological components (such as enzymes, genetic circuits, metabolic pathways and cells) and redesign existing biological systems (11). Furthermore, synthetic biology can be modeled, under- stood, and tuned to meet particular performance criteria, and smaller components can be assembled into larger inte- grated systems that solve speciﬁc problems (11). Hence, more bioinformatics tools have been created recently for applications in metabolic engineering. Since 1995, Kanehisa et al. has been developing knowl- edge-based methods for elucidating higher-order systemic behaviors of cells and organisms from genomic and molec- ular information (12–15). They established the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for integrating genomic, chemical, metabolic pathways, and systemic functional information (12–15). MetaCyc (16) is a non-redundant database and contains more than 1100 experimentally elucidated metabolic pathways from more than 1500 organisms; it provides a set of reference data for computationally predicting metabolic pathways. Several important databases of metabolic path- ways exist with hundreds of metabolic pathways and thou- sands of biochemical reactions; even the metabolic pathways for a small organism constitutes a large net- work, such as Roche Applied Science Biochemical Pathways chart (17) and BRENDA (18). Although numerous servers can reconstruct metabolic pathways *To whom correspondence should be addressed. Tel: +886 3 5712121. ext.: 56952; Fax: +886 3 5739320; Email: bryan@mail.nctu.edu.tw The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. 2009 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.