MODULATING THE BIOSYNTHESIS OF A BIOACTIVE STEROIDAL SAPONIN, CHOLESTANOL GLUCOSIDE BY LASIODIPLODIA THEOBROMAE USING ABIOTIC STRESS FACTORS
Keywords:Secondary metabolites, Cholestanol glucoside, Filamentous fungi, Lasiodiplodia theobromae, Abiotic stress
Objective: The present study investigates the modulation of cholestanol glucoside (CG) biosynthesis by Lasiodiplodia theobromae in response to oxidative, osmotic and heat shock stresses.
Methods: The fungal cultures were subjected to oxidative stress by supplementing the culture media with menadione or H2O2 to the desired final concentrations. Osmotic stress was implemented by the addition of the desired concentrations of NaCl or sorbitol. For heat-shock treatments, the fungal cultures were subjected to required temperature variations. Each stress treatment was carried out at different time points so as to include different stages of fungal growth.
Results: Oxidative stress enhanced CG yield by the fungus by 1.8-fold (88.3Â±0.6 mg/l) where as osmotic and heat shock stresses proved to be poor enhancers of CG production.
Conclusions: Our findings enable a cost-effective, large scale production of CG by L. theobromae and more over throws light on the possible antioxidant activity of the compound in the organism.
Riquelme M. Tip growth in filamentous fungi: a road trip to the apex. Annu Rev Microbiol 2013;67:587-609.
Brakhage AA. Regulation of fungal secondary metabolism. Nat Rev Microbiol 2013;11:21-32.
Jeong JC, Lee IY, Kim SW, Park YH. Stimulation of Î²-carotene synthesis by hydrogen peroxide in Blakeslea trispora. Biotechnol Lett 1999;21:683-6.
Kavitha S, Chandra TS. Effect of vitamin E and menadione supplementation on riboflavin production and stress parameters in Ashbya gossypii. Process Biochem 2009;44:934-8.
NÃ¼tzmann HW, Schroeckh V, Brakhage AA. Regulatory cross talk and microbial induction of fungal secondary metabolite gene clusters. Methods Enzymol 2011;517:325-41.
Jinu MV, Gini CK, Jayabaskaran C. In vitro antioxidant activity of cholestanol glucoside from an endophytic fungus, Lasiodiplodia theobromae isolated from Saraca asoca. J Chem Pharm Res 2015;7:952-62.
Tan RX, Zou WX. Endophytes: a rich source of functional metabolites. Nat Prod Rep 2001;18:448-59.
Bode HB, Bethe B, HÃ¶fs R, Zeeck A. Big effects from small changes: possible ways to explore nature's chemical diversity. Chem Biochem 2002;3:619-27.
Bills GF, Platas G, Fillola A, Jimenez MR, Collado J, Vicente F, et al. Enhancement of antibiotic and secondary metabolite detection from filamentous fungi by growth on nutritional arrays. J Appl Microbiol 2008;104:1644-58.
Mohanty SS, Prakash S. Effects of culture media on larvicidal property of secondary metabolites of mosquito pathogenic fungus Chrysosporium lobatum (Moniliales: Moniliaceae). Acta Trop 2009;109:50-4.
Montibus M, Pinson-Gadais L, Richard-Forget F, Barreau C, Ponts N. Coupling of transcriptional response to oxidative stress and secondary metabolism regulation in filamentous fungi. Crit Rev Microbiol 2013;0:1-14.
Roze LV, Chanda A, Wee J, Awad D, Linz JE. Stress-related transcription factor AtfB integrates secondary metabolism with oxidative stress response in Aspergilli. J Biol Chem 2011;286:35137-48.
Duran R, Cary JW, Calvo AM. Role of the osmotic stress regulatory pathway in morphogenesis and secondary metabolism in filamentous fungi. Toxins 2010;2:367-81.
Deduke C, Timsina B, Piercey-Normore MD. Effect of environmental change on secondary metabolite production in lichen-forming fungi. In: Dr. Stephen Young editor. International perspectives on global environmental change. 1st ed. Europe: INTECH Open Access Publisher; 2012. p. 197-230.
Edreva A, Velikova V, Tsonev T, Dagnon S, GÃ¼rel A, AktaÅŸ L, et al. Stress-protective role of secondary metabolites: diversity of functions and mechanisms. Gen Appl Plant Physiol 2008;34:67-78.
Zhang CH, Fevereiro PS, He G, Chen Z. Enhanced paclitaxel productivity and release capacity of Taxus chinensis cell suspension cultures adapted to chitosan. Plant Sci 2007;172:158-63.
Do CB, Cormier F. Effects of low nitrate and high sugar concentrations on anthocyanin content and composition of grape (Vitis vinifera L.) cell suspension. Plant Cell Rep 1991;9:500-4.
Godoy-HernÃ¡ndez GC, VÃ¡zquez-Flota FA, Loyola-Vargas VM. The exposure to trans-cinnamic acid of osmotically stressed Catharanthus roseus cells cultured in a 14-L bioreactor increases alkaloid accumulation. Biotechnol Lett 2000;22:921-5.
Zhao J, Hu Q, Guo YQ, Zhu WH. Effects of stress factors, bioregulators, and synthetic precursors on indole alkaloid production in compact callus clusters cultures of Catharanthus roseus. Appl Microbiol Biotechnol 2001;55:693-8.
Kavitha S, Chandra TS. Vitamin C modulates metabolic responses in hemiascomycete riboflavinogenic fungus Ashbya gossypii. Int J Curr Microbiol App Sci 2014;3:161-70.
Agastian P, Merlin JN, Christhudas IN, Kumar P. Optimization of growth and bioactive metabolite production: Fusarium solani. Asian J Pharm Clin Res 2013;6:98-103.
Mathan S, Subramanian V, Nagamony S. Optimization and antimicrobial metabolite production from endophytic fungi Aspergillus terreus KC 582297. Eur J Exp Biol 2013;3:138-44.
Keller NP, Turner G, Bennett JW. Fungal secondary metabolismâ€”from biochemistry to genomics. Nat Rev Microbiol 2005;3:937-47.
Fox EM, Howlett BJ. Secondary metabolism: regulation and role in fungal biology. Curr Opin Microbiol 2008;11:481-7.
Faried, A, Faried LS, Hashimoto S, Tsuboi K, Asao T, Kuwano H, Yazawa S. Evaluation of novel glycoconjugates molecules as promising anti-cancer agents. Angiogenesis Cancer Vasc Dis 2006;17:38-103.
Faried A, Faried LS, Nakagawa T, Yamauchi T, Kitani M, Sasabe H, et al. Chemically synthesized sugarâ€cholestanols possess a preferential anticancer activity involving promising therapeutic potential against human esophageal cancer. Cancer Sci 2007;98:1358-67.
Hahismoto S, Yazawa S, Asao T, Faried A, Nishimura T, Tsuboi K, et al. Novel sugar-cholestanols as anticancer agents against peritoneal dissemination of tumor cells. Glycoconjugate J 2008;25:531-44.
Betina V. Differentiation and secondary metabolism in some prokaryotes and fungi. Folia Microbiol 1995;40:51-67.
Angelova MB, Pashova SB, Spasova BK, Vassiley SV, Slokoska LS. Oxidative stress response of filamentous fungi induced by hydrogen peroxide and paraquat. Mycol Res 2005;109:150-8.
Kavitha S, Chandra TS. Oxidative stress protection and glutathione metabolism in response to hydrogen peroxide and menadione in riboflavinogenic fungus ashbya gossypii. Appl Biochem Biotechnol 2014;174:2307-25.
Zheng W, Zhao Y, Zhang M, Wei Z, Miao K, Sun W. Oxidative stress response of Inonotus obliquus induced by hydrogen peroxide. Med Mycol 2009;47:814-23.
Ponts N, Pinson-Gadais L, Verdal-Bonnin MN, Barreau C, Richard-Forget F. Accumulation of deoxynivalenol and its 15-acetylated form is significantly modulated by oxidative stress in liquid cultures of Fusarium graminearum. FEMS Microbiol Lett 2006;258:102-7.
Jayashree T, Subramanyam C. Oxidative stress as a prerequisite for aflatoxin production by Aspergillus parasiticus. Free Radical Biol Med 2000;29:981-5.