Understanding alternative fluxes/effluxes through comparative metabolic pathway analysis of phylum actinobacteria using a simplified approach.
Actinobacteria are known for their diverse metabolism and physiology. Some are dreadful human pathogens whereas some constitute the natural flora for human gut. Therefore, the understanding of metabolic pathways is a key feature for targeting the pathogenic bacteria without disturbing the symbiotic ones. A big challenge faced today is multiple drug resistance by Mycobacterium and other pathogens that utilize alternative fluxes/effluxes. With the availability of genome sequence, it is now feasible to conduct the comparative in silico analysis. Here we present a simplified approach to compare metabolic pathways so that the species specific enzyme may be traced and engineered for future therapeutics. The analyses of four key carbohydrate metabolic pathways, i.e., glycolysis, pyruvate metabolism, tri carboxylic acid cycle and pentose phosphate pathway suggest the presence of alternative fluxes. It was found that the upper pathway of glycolysis was highly variable in the actinobacterial genomes whereas lower glycolytic pathway was highly conserved. Likewise, pentose phosphate pathway was well conserved in contradiction to TCA cycle, which was found to be incomplete in majority of actinobacteria. The clustering based on presence and absence of genes of these metabolic pathways clearly revealed that members of different genera shared identical pathways and, therefore, provided an easy method to identify the metabolic similarities/differences between pathogenic and symbiotic organisms. The analyses could identify isoenzymes and some key enzymes that were found to be missing in some pathogenic actinobacteria. The present work defines a simple approach to explore the effluxes in four metabolic pathways within the phylum actinobacteria. The analysis clearly reflects that actinobacteria exhibit diverse routes for metabolizing substrates. The pathway comparison can help in finding the enzymes that can be used as drug targets for pathogens without effecting symbiotic organisms within the same host. This may help to prevail over the multiple drug resistance, for designing broad spectrum drugs, in food industries and other clinical research areas.
Molecular Biology Laboratory, Department of Zoology, University of Delhi, Delhi-110 007, India; Department of Zoology, Sri Venkateswara College, University of Delhi South Campus, New Delhi-110 021, India.
Mansi
M
Verma
Devi
D
Lal
Anjali
A
Saxena
Shailly
S
Anand
Jasvinder
J
Kaur
Jaspreet
J
Kaur
Rup
R
Lal
D019342:Acetic Acid / Q000378:metabolism; D039903:Actinobacteria / Q000235:genetics* / Q000378:metabolism*; D050260:Carbohydrate Metabolism / Q000235:genetics*; D002952:Citric Acid Cycle / Q000235:genetics; D016000:Cluster Analysis; D032882:Comprehension; D019295:Computational Biology / Q000379:methods*; D006019:Glycolysis / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008954:Models, Biological; D010427:Pentose Phosphate Pathway / Q000235:genetics; D010802:Phylogeny; D019289:Pyruvic Acid / Q000378:metabolism
D019289:Pyruvic Acid; D019342:Acetic Acid
Actinobacteria; Fluxes/effluxes; Glycolysis; KEGG; Kyoto Encyclopedia of Genes and Genomes; MVSP; Metabolic pathway; Multivariate Statistical Package; NAD+; NADPH; PEP; PRPP; nicotinamide adenine dinucleotide; nicotinamide adenine dinucleotide phosphate dehydrogenase; phosphoenol pyruvate; phosphoribosyl pyrophosphate