Open Access Research article

Global genome analysis of the shikimic acid pathway reveals greater gene loss in host-associated than in free-living bacteria

Jurica Zucko12, Walter C Dunlap3, J Malcolm Shick4, John Cullum1, François Cercelet56, Bijal Amin5, Lena Hammen57, Timothy Lau5, Jamal Williams5, Daslav Hranueli2 and Paul F Long5*

Author Affiliations

1 Department of Genetics, University of Kaiserslautern, Postfach 3049, 67653 Kaiserslautern, Germany

2 Section for Bioinformatics, Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia

3 Centre for Marine Microbiology and Genetics, Australian Institute of Marine Science, PMB 3 Townsville MC, Townsville, Queensland, 4810 Australia

4 School of Marine Sciences, University of Maine, 5751 Murray Hall, Orono, ME 04469-5751 USA

5 The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK

6 Department of Bioengineering, Polytech'Nice-Sophia, 930 Route des Colles, 145-06903, Sophia Antipolis, Cedex, France

7 Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany

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BMC Genomics 2010, 11:628  doi:10.1186/1471-2164-11-628

Published: 11 November 2010



A central tenet in biochemistry for over 50 years has held that microorganisms, plants and, more recently, certain apicomplexan parasites synthesize essential aromatic compounds via elaboration of a complete shikimic acid pathway, whereas metazoans lacking this pathway require a dietary source of these compounds. The large number of sequenced bacterial and archaean genomes now available for comparative genomic analyses allows the fundamentals of this contention to be tested in prokaryotes. Using Hidden Markov Model profiles (HMM profiles) to identify all known enzymes of the pathway, we report the presence of genes encoding shikimate pathway enzymes in the hypothetical proteomes constructed from the genomes of 488 sequenced prokaryotes.


Amongst free-living prokaryotes most Bacteria possess, as expected, genes encoding a complete shikimic acid pathway, whereas of the culturable Archaea, only one was found to have a complete complement of recognisable enzymes in its predicted proteome. It may be that in the Archaea, the primary amino-acid sequences of enzymes of the pathway are highly divergent and so are not detected by HMM profiles. Alternatively, structurally unrelated (non-orthologous) proteins might be performing the same biochemical functions as those encoding recognized genes of the shikimate pathway. Most surprisingly, 30% of host-associated (mutualistic, commensal and pathogenic) bacteria likewise do not possess a complete shikimic acid pathway. Many of these microbes show some degree of genome reduction, suggesting that these host-associated bacteria might sequester essential aromatic compounds from a parasitised host, as a 'shared metabolic adaptation' in mutualistic symbiosis, or obtain them from other consorts having the complete biosynthetic pathway. The HMM results gave 84% agreement when compared against data in the highly curated BioCyc reference database of genomes and metabolic pathways.


These results challenge the conventional belief that the shikimic acid pathway is universal and essential in prokaryotes. The possibilities that non-orthologous enzymes catalyse reactions in this pathway (especially in the Archaea), or that there exist specific uptake mechanisms for the acquisition of shikimate intermediates or essential pathway products, warrant further examination to better understand the precise metabolic attributes of host-beneficial and pathogenic bacteria.