Microbial mediated drug metabolism

A recent publication out from our lab. 
A novel approach for the prediction of species-specific biotransformation of xenobiotic/drug molecules by the human gut microbiota

Abstract
The human gut microbiota is constituted of a diverse group of microbial species harbouring an enormous metabolic potential, which can alter the metabolism of orally administered drugs leading to individual/population-specific differences in drug responses. Considering the large heterogeneous pool of human gut bacteria and their metabolic enzymes, investigation of species-specific contribution to xenobiotic/drug metabolism by experimental studies is a challenging task. Therefore, we have developed a novel computational approach to predict the metabolic enzymes and gut bacterial species, which can potentially carry out the biotransformation of a xenobiotic/drug molecule. A substrate database was constructed for metabolic enzymes from 491 available human gut bacteria. The structural properties (fingerprints) from these substrates were extracted and used for the development of random forest models, which displayed average accuracies of up to 98.61% and 93.25% on cross-validation and blind set, respectively. After the prediction of EC subclass, the specific metabolic enzyme (EC) is identified using a molecular similarity search. The performance was further evaluated on an independent set of FDA-approved drugs and other clinically important molecules. To our knowledge, this is the only available approach implemented as ‘DrugBug’ tool for the prediction of xenobiotic/drug metabolism by metabolic enzymes of human gut microbiota.

Please explore and write back to me (ashoks773@gmail.com) in case of any problem. Comments are welcome.

Databases and tools for understanding the xenobiotics metabolism

Human physiology influenced by human microbiome in several ways, mainly via impact of human gut microbes on the metabolism of xenobiotic compounds. These interactions are quite important as they are very significant in order to improve overall efficacy of therapeutic compounds, but microbial metabolism of xenobiotics still remains unexplored. Here, I have provided the link of important databases and tools for biotransformation/degradation of xenobiotics. 

1. The Transformer database: biotransformation of xenobiotics

Available at: http://bioinformatics.charite.de/transformer/index.php?site=faq

http://nar.oxfordjournals.org/content/42/D1/D1113.full

2. UM-BBD -- University of Minnesota Biocatalysis/Biodegradation Database

Available at: http://www.hsls.pitt.edu/obrc/index.php?page=URL1100188151

http://www.ncbi.nlm.nih.gov/pubmed/19767608

http://www.microbialinformaticsj.com/content/2/1/1   

3. Eawag: Biocatalytic/Biodegradation database, to identify the metabolic enzyme for candidate drug

http://eawag-bbd.ethz.ch/predict/

4. Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes

http://pharmacomicrobiomics.com/

http://www.gutpathogens.com/content/4/1/16

5. DrugBank 4.0: shedding new light on drug metabolism

http://www.drugbank.ca/

http://nar.oxfordjournals.org/content/early/2013/11/06/nar.gkt1068.full