Ferdowsi University of Mashhad

Document Type : Research Articles


1 Ferdowsi University of mashhad, Mashhad, Iran

2 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

3 Pharmacognosi Department, Pharmacology School, Medical Science University of Mashhad, Mashhad, Iran

4 Department of Crop Biotechnology and Breeding Faculty of Agriculture

5 Chemistry Department, Science school, Gonbad university, Gonbad, Iran



Endophytic fungi are often producing host plant secondary metabolites. Tanshinones are secondary metabolites of the Salvia genus which also produced by some endophytic fungi. Efficient secondary metabolite production in endophytic fungi drops significantly after sequential subcultures. 5-azacytidine (5-AC) is an analog of the naturally occurring pyrimidine nucleoside cytidine and a DNA methyltransferase inhibitor. In this relation, 5-AC is an effective tool to induce expression of silenced secondary metabolite genes in endophytic fungi. In this experiment we isolated 4 endophytic fungi from the roots of Salvia abrotanoides which produced tanshinone. Cryptotanshinone and tanshinon IIA were produced by Penicillium canescens, Penicillium nodositatum, and Penicillium pinophilum, while Paraphoma radicina only produced tanshinon IIA. The maximum amount of tanshinones was extracted from P. pinophilum culture with 130.826 mg cryptotanshinone /g of dry weight and also 50.155 mg Tanshinone IIA/g of dry weight. These amounts were significantly more than the tanshinones produced in plant roots (0.55 mg cryptotanshinone/g of dry weight, 1.3 mg Tanshinone IIA/g of dry weight). In third subculture, tanshinone production decreased significantly. 5-azacytidine as an epigenetic modifier retrieved tanshinone production in 3d subculture of P. pinophilum. Also, 5- azacytidine treatment made a big jump in Tanshinone IIA production in P. radicina (63.176 mg TIIA/g of dry weight) besides increasing Tanshinone IIA production in P. nodositatum cultures. This is the first report using 5- azacytidine to improve tanshinone production in endophytic fungi. Our results confirm that 5- azacytidine is an efficient, easy, and quick chemical to elicitate secondary metabolite production in endophytic fungi.