Production and bioprocess optimization of antitumor Epothilone B analogue from Aspergillus fumigatus, endophyte of Catharanthus roseus, with response surface methodology.

Epothilones are secondary metabolites produced by Sorangium cellulosum with powerful antiproliferative activity against tumor cells by stabilizing their microtubule arrays, arresting their cellular division at G2-M phase. Unfortunately, the lower yield of epothilone is the challenge for its higher accessibility, thus, searching for alternative sources with promising epothilone producing potency is the prospective. Endophytic fungi are the potential repertoire for bioactive metabolites, thus exploring the epothilone producing potency of endophytic fungi of medicinal plants was objective. Thirty-two fungal isolates were recovered from the tested medicinal plants and their potency to produced epothilone have been assessed using the TLC, HPLC and molecular markers epoA, epoC and epoK. Aspergillus fumigatus EFBL, an endophyte of Catharanthus roseus, was the potent epothilone producer (21.5 μg/g biomass) as revealed from the chromatographic analyses and PCR of molecular markers. The chemical identity of extracted epothilone was verified from the HPLC, NMR, FTIR and LC-MS analyses as epothilone B analogue. The putative epoA gene from A. fumigatus was amplified using RT-PCR with the conservative corresponding primers to the active-sites of S. cellulosum. The amplicons of epoA was 517 bp displayed 98 % similarity with A. fumigatus PKS-NRPS domains, and 40 % similarity with epoA of S. cellulosum. From the in silico analyses, Val

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