OxDBase: a database of oxygenases involved in biodegradation
© Jain et al; licensee BioMed Central Ltd. 2009
Received: 21 November 2008
Accepted: 30 April 2009
Published: 30 April 2009
Oxygenases belong to the oxidoreductive group of enzymes (E.C. Class 1), which oxidize the substrates by transferring oxygen from molecular oxygen (O2) and utilize FAD/NADH/NADPH as the co-substrate. Oxygenases can further be grouped into two categories i.e. monooxygenases and dioxygenases on the basis of number of oxygen atoms used for oxidation. They play a key role in the metabolism of organic compounds by increasing their reactivity or water solubility or bringing about cleavage of the aromatic ring.
We compiled a database of biodegradative oxygenases (OxDBase) which provides a compilation of the oxygenase data as sourced from primary literature in the form of web accessible database. There are two separate search engines for searching into the database i.e. mono and dioxygenases database respectively. Each enzyme entry contains its common name and synonym, reaction in which enzyme is involved, family and subfamily, structure and gene link and literature citation. The entries are also linked to several external database including BRENDA, KEGG, ENZYME and UM-BBD providing wide background information. At present the database contains information of over 235 oxygenases including both dioxygenases and monooxygenases. This database is freely available online at http://www.imtech.res.in/raghava/oxdbase/.
OxDBase is the first database that is dedicated only to oxygenases and provides comprehensive information about them. Due to the importance of the oxygenases in chemical synthesis of drug intermediates and oxidation of xenobiotic compounds, OxDBase database would be very useful tool in the field of synthetic chemistry as well as bioremediation.
In the last few decades, extensive urbanization and rapid industrialization has resulted in the addition of a large number of xenobiotic compounds into the environment. The chemical properties and quantities of the xenobiotic compounds determine their toxicity and persistence in the environment. Organic (aromatic/non-aromatic) compounds constitute a major group of environmental pollutants . These compounds are highly persistent in the environment due to their thermodynamic stability . Many of these compounds have been reported to be toxic to the living organisms . Increased public awareness about the hazards and toxicity of these compounds has encouraged the development of technologies for their remediation. Bioremediation, which utilizes the microbial metabolic potential of the degrading microorganisms, has come up as an efficient and cost-effective means of large scale removal of these compounds in comparison to the physico-chemical means of bioremediation. A number of bacteria that can degrade a variety of aromatic compounds have been identified and the pathways involved in the degradation have been extensively characterized [3, 4]. Based on the complexity of the degradation pathways, the phenomenon of biodegradation is categorized into two types: convergent and divergent modes of degradation (Fig. 1). In the convergent mode, structurally diverse aromatic compounds are converted to one of a few aromatic ring cleavage substrates such as catechol, gent sate, protocatechuate and their derivatives . Peripheral enzymes, particularly oxygenases and dehydrogenases, were found to transform structurally diverse substrates into one of these central intermediates by bringing about the hydroxylation of the aromatic nucleus (Fig. 2A), and hence it is thought that bacteria have developed these enzymes to extend their substrate range . There are a number of benefits of channeling diverse compounds into a few central aromatic ring cleavage substrates; the foremost among these being reduction of genetic load and simplification of regulatory circuits. Further, the centralized degradation pathways mean synthesis of fewer degradative enzymes requiring less metabolic energy. This is clearly a major advantage to soil microbes which often find themselves in unfavorable environments containing low concentrations of carbon sources suitable for growth . However, further conversion of these intermediates into tricarboxylic acid (TCA) cycle intermediates was found to be highly diverged (divergent mode) (Fig. 1). In this divergent mode, a metal-dependent dioxygenase channels these dihydroxylated intermediates into one of the two possible pathways: the meta-cleavage pathway or the ortho-cleavage pathway [7–9] (Fig. 1). The substrate specificity of these metal-dependent dioxygenases has been found to play a key role in the overall determination of pathway selection  and the dioxygenases have been grouped into two classes namely extradiol and intradiol dioxygenases . Extradiol dioxygenases have nonheme iron (II) at their active site and catalyze ring cleavage at the carbon-carbon (C-C) bond adjacent to the vicinal hydroxyl groups (meta-cleavage) (Fig. 2B) whereas intradiol dioxygenases have non-heme iron (III) in their active site and catalyze ring cleavage at the C-C bond between the vicinal hydroxyl groups (ortho-cleavage) (Fig. 2C). Extradiol dioxygenases channel substrates into a meta-pathway whereas intradiol dioxygenases channel these substrates into an ortho-pathway. Similarly, monoxygenases catalyze the transfer of one atom of molecular oxygen to the organic compound with other being reduced by electrons from cofactors to yield water thereby increasing their reactivity and water solubility.
Database design and development
Data content and scope
Description and content of fields associated with each entry of OxDBase database.
Wherever possible IUBMB Name or common name of the enzyme
Chemical nature of substrate of dioxygenase
Specificity and nature of oxidation of dioxygenase
The Enzyme Commissions identification (EC) number, link to the SWISS PROT ENZYME database
The EC number and link to the BRENDA Enzyme information system
Link to molecular interaction network of Kyoto Encyclopedia of Genes and Genomes (KEGG) along with EC number
The accession number of University of Minnesota Biocatalysis/biodegradation database
The name and chemical structure of substrate and product
Popular names other than the IUBMB
Link to the NCBI Entrez-gene database
PDB four letter identification code plus a link to the corresponding information
Link to the relevant literature to the PubMed database
Categorization and classification of data
All entries of OxDBase are divided into two broad classes i.e. monooxygenases and dioxygenases depending on the number of atomic oxygen used during oxidation. On the basis of their mode of action dioxygenases are further categorized into aromatic ring cleavage dioxygenase (ARCD) and aromatic ring hydroxylating dioxygenase (ARHD) . Depending upon the position of ring cleavage with respect to the hydroxyl groups, ARCDs are again divided into intradiol aromatic ring cleaving dioxygenase (IARCD) and extradiol aromatic ring cleavage dioxygenase (EARCD).
Searching the database
OxDBase provides a number of methods to search the database. The following are the major ways: (i) generalized search using keywords to search in all fields of database; (ii) The Enzyme Commission number (EC number) based searching that allows extraction of a unique OxDBase entry; and (iii) class based searching which restricts the search within a specified class (described in categorization and classification of enzymes).
Potential utility and limitations
At present, OxDBase has 237 entries of distinct oxygenases. Among them, 118 belong to monooxygenases and 119 related to dioxygenases. The primary aim of OxDBase is to provide detailed information of all known oxygenases because of their wide use in synthetic chemistry and bioremediation. Hence, inspite of the limited information available about oxygenases, OxDBase is largely complete and of considerable importance. As new data becomes available, the database will also increase in size.
Submission and updation of OxDBase
OxDBase is a unique database which provides comprehensive information about oxygenases. It is a platform from which users can easily retrieve information on all available oxygenases. The present database would increase our understanding of the biological, biochemical, genomic, evolutionary and structural properties of oxygenases that could be exploited for industrial and bioremediation applications.
As regards to the future work the database needs to be maintained and developed further, ensuring the links to all external databases remain correct and newly published data is added. We hope, over the time, database size will increase with accumulation of more experimental information. In addition we also hope that data compilation and distribution through a publicly available medium will help in biodegradation research.
Availability and requirements
OxDBase is freely available at http://www.imtech.res.in/raghava/oxdbase/.
List of abbreviations used
Flavin Adenine Dinucleotide
Nicotinamide Adenine Dinucleotide Reduced
Nicotinamide Adenine Dinucleotide Phosphate Reduced
Practical Extraction and Report Language
National Center for Biotechnology Information
Protein Data Bank.
The Comprehensive Enzyme Information System
University of Minnesota Biocatalysis/Biodegradation Database
International Union of Biochemistry and Molecular Biology
Kyoto Encyclopedia of Genes and Genomes
Enzyme Nomenclature Database.
We are thankful to our Bioinformatics Centre for excellent technical help. Authors are thankful to Council of Scientific and Industrial Research (CSIR) and Department of Biotechnology (DBT), Govt. of India for financial support. This is IMTECH communication number 050/2008.
- Dagley S: Biochemistry of aromatic hydrocarbon degradation in Pseudomonads. The Bacteria. Edited by: Sokatch J, Ornstone LN. 1986, Academic Press, Orlando, 10: 527-555.
- Díaz E, Ferrández A, Prieto MA, García JL: Biodegradation of aromatic compounds by Escherichia coli. Microbiol Mol Biol Rev. 2001, 65: 523-69. 10.1128/MMBR.65.4.523-569.2001.PubMed CentralView ArticlePubMed
- Diaz E: Bacterial degradation of aromatic pollutants: a paradigm of metabolic versatility. Int Microbiol. 2004, 7: 173-180.PubMed
- Timmis KN, Steffan RJ, Untermann R: Designing microorganisms for the treatment of toxic wastes. Ann Rev Microbiol. 1994, 48: 525-557. 10.1146/annurev.mi.48.100194.002521.View Article
- Meer van der JR, de Vos WM, Harayama S, Zehnder AJB: Molecular mechanisms of genetic adaptation to xenobiotic compounds. Microbiol Rev. 1992, 56: 677-694.PubMed CentralPubMed
- Harayama S, Mermod N, Rekik M, Lehrbach PR, Timmis KN: Roles of the divergent branches of the meta-cleavage pathway in the degradation of benzoate and substituted benzoates. J Bacteriol. 1987, 169: 558-564.PubMed CentralPubMed
- Harayama S, Rekik M: Bacterial aromatic – ring cleavage are classified into two different families. J Biol Chem. 1989, 264: 15328-15333.PubMed
- Eltis LD, Bolin JT: Evolutionary relationships among extradiol dioxygenases. J Bacteriol. 1996, 178: 5930-5937.PubMed CentralPubMed
- Takami H, Kudo T, Horikoshi K: Isolation of extradiol dioxygenase genes that are phylogenetically distant from other metacleavage dioxygenase genes. Biosci Biotechnol Biochem. 1997, 61: 530-532.View ArticlePubMed
- Vaillancourt FH, Bolin JT, Eltis LD: The ins and outs of ring-cleaving dioxygenases. Crit Rev Biochem Mol Biol. 2006, 41: 241-267. 10.1080/10409230600817422.View ArticlePubMed
- Novotna J, Honzatko A, Bednar P, Kopecky J, Janata J, Spizek JL: 3,4-Dihydroxyphenyl alanine-extradiol cleavage is followed by intramolecular cyclization in lincomycin biosynthesis. Eur J Biochem. 2004, 271: 3678-3683. 10.1111/j.1432-1033.2004.04308.x.View ArticlePubMed
- Gibson DT, Parales RE: Aromatic hydrocarbon dioxygenases in environmental biotechnology. Curr Opin Biotechnol. 2000, 11: 236-243. 10.1016/S0958-1669(00)00090-2.View ArticlePubMed
- van Beilen JB, Duetz WA, Schmid A, Witholt B: Practical issues in the application of oxygenases. Trends Biotechnol. 2003, 21: 170-7. 10.1016/S0167-7799(03)00032-5.View ArticlePubMed
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.