Screening Endophytic Fungi for Production of Histone Deacetylase Inhibitors

Abstract

HDAC inhibitors demonstrate anti-neoplastic effects by inhibiting cell migration, inducing growth arrest and programmed cell death. HDAC activity can be inhibited by certain natural dietary sources such as dietary fibres, vegetables (cruciferous vegetables), whole grains (parsley, celery), fruits (grapes, blueberries etc.) and certain micronutrients. Endophytic fungi are microorganisms which colonize inside plant tissue without causing apparent harm to the host. Besides upon colonization of host plant endophytes synthesize an array of secondary metabolite which may defend the host plant against survival and stress conditions and in turn the host plant supply nutrients and habitat for endophytic fungi. Therefore, in addition to interaction of endophytes with the host plant, endophyte acquires the property of their host plant and start producing analogue bioactive compounds which have medicinal value. The current study reports the exploration of endophytic fungi isolated from R. serpentine, C. camphora, C. zeylanicum, C. roseus, Taxusbaccata, A. marmelos, Vitisvinifera, C. malabaricum, M. pumila for their potential to produce HDAC inhibitors. In the proposed study culture filtrate of endophytic fungi obtained from potato dextrose broth were screened for Biochemical assays namely: Acetic Acid Standard Test (K-ACET, Megazyme) was used for the identification, where out of 80 endophytic isolates, only 21 isolates were found to exhibit >75% activity among which 2 isolates were selected with >99% activity and subjected to mass production. These were subsequently extracted in four different solvents and again tested for presence of HDAC inhibitors. Hexane extract of #23CZSTITG and EA extract of #40CMBLRT were found to be potent producer of HDAC inhibitors. The potent producers of HDAC inhibitors from endophytic isolates #23CZSTITG and #40CMBLRT, were tentatively identified as Botryosphaeria sp. and Penicillium sp. respectively. The genomic DNA of the selected isolates were extracted, amplified and further send for sequencing for molecular identification.