Flux Balance Analysis: An Insilico Analysis of Staphylococcus aureus Cell Wall Biosynthesis Pathway Metabolism

Staphylococcus aureus is now being considered under investigation for designing of new inhibitors as the pathogen has acquired resistance against β lactam antibiotics. S. aureus is acquiring resistance against β lactam antibiotics because of penicillin binding proteins (PBPs) coded by mec A gene. These PBPs are considered to be responsible for peptidoglycan cell wall biosynthesis. The peptidoglycan cell wall biosynthesis has therefore been targeted for drug targets identification. Recent researches proved that pathway could be inhibited by drugs like Vancomycin, Daptomycin. Here study has been made to apply insights of Flux Balance analysis(FBA) for peptidoglycan cell wall biosynthesis for identifying antimicrobial drug targets.A comprehensive model of peptidoglycan biosynthesis pathway involves 42 metabolites participating in 13 reactions which are catalysed by 17 proteins. FBA studies has been made for this particular pathway model involving insilico gene deletions and inhibition of PBP2 by analogues of Hamamelitannin (2´, 5-di-O-galloyl-D-hamamelose)a plant product from Hamamelis virginiana. The study provided hints about proteins essential for pathway further leading to rational identification of possible drug targets. The analysis showed that apart from PBP2, potential drug targets mtgA, murj(mvin), glycosyltransferase, mrca/B, mrdA, pbpB, p bp4 identified are correlated well with previous researches. This study has helped in rational identification of potential antimicrobial drug targets with application of FBA.