Biosynthetic Pathway Determination for Intermediatory Enrichment Fragments between Plant Products and drugs

Abstract

Fragment based approaches have been proved to be efficacious in the drug discovery process. The fragmentation of drug leads into smaller pieces, or even into discrete functional can be useful to simplify the computational analysis of ligand binding and to map out different pharmacophoric elements required for high-affinity binding [1]. An ideal fragment is chemically diverse, structurally less complex; possess aqueous solubility and high availability [2]. These fragments can then be elaborated, combined with other molecules to provide novel drug leads. Natural products are the most popular source of drug leads. Exploiting the natural sources has now become the greatest interest of pharmaceutical industries for discovery of new leads. Genetic manipulations of micro-organisms or metabolic engineering have now been seen as a striking innovation in the natural product drug discovery process pathways leading to efficient production of drugs and drug precursors [3]. Alteration of natural pathways in organism leads to increased titer and production in the most inexpensive way [4]. In this study, we are investigating the fragments that are significantly enriched between plant products and known drug compounds and identify the biosynthesis pathway with the enriched fragment as an intermediate. A pipeline has been developed to engineer the enriched fragments in living organisms such as E.coli, Arabidopsis thaliana, Pea sativum etc. Once the fragments from the natural sources have been obtained, further scope of this research is to find all possible pathways which yield compounds with therapeutic activities (drugs) using the enriched fragment as the starting material in microorganisms.