Abstract
Endophytic fungi are rich sources of structurally complex chemical scaffolds with interesting biological activities. However, their metabolome is still unknown, making them appealing for novel compound discovery. To maximize the number of secondary metabolites produced from a single microbial source, we used the “OSMAC (one strain–many compounds) approach.” In potato dextrose medium, M. phaseolina produced phomeolic acid (1), ergosterol peroxide (2), and a volatile compound 1,4-benzene-diol. Incorporating an epigenetic modifier, sodium valproate, affected the metabolite profile of the fungus. It produced 3-acetyl-3-methyl dihydro-furan-2(3H)-one (3) and methyl-2-(methyl-thio)-butyrate (4), plus volatile chemicals: butylated hydroxy toluene (BHT), di-methyl-formamide, 3-amino-1-propanol, and 1,4-benzenediol, 2-amino-1-(O-methoxyphenyl) propane. The structure of compounds 1–4 was established with the help of spectroscopic data. This study revealed first-time compounds 1–4 in the fungus M. phaseolina using a classical and epigenetic manipulation approach.
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Adpressa DA, Stalheim KJ, Proteau PJ et al (2017) Unexpected biotransformation of the HDAC inhibitor vorinostat yields aniline-containing fungal metabolites. ACS Chem Biol 12:1842–1847. https://doi.org/10.1021/acschembio.7b00268
Alves E, Lucas GC, Pozza EA et al (2013) Scanning electron microscopy for fungal sample examination. In: Gupta VK, Tuohy MG, Ayyachamy M et al (eds) Laboratory protocols in fungal biology: current methods in fungal biology. Springer, New York, NY, USA, pp 133–150
Choi J-H, Suzuki T, Okumura H et al (2014) Endoplasmic reticulum stress suppressive compounds from the edible mushroom Mycoleptodonoides aitchisonii. J Nat Prod 77:1729–1733. https://doi.org/10.1021/np500075m
de Souza TJ, SrA B, Apel MA (2017) A chemometrics approach to the investigation of the intraspecific variability of the volatile oil of Eupatorium tremulum from Southern Brazil. J Nat Prod 80:45–52. https://doi.org/10.1021/acs.jnatprod.6b00313
Du X, Song M, Rouseff R (2011) Identification of new strawberry sulfur volatiles and changes during maturation. J Agric Food Chem 59:1293–1300. https://doi.org/10.1021/jf104287b
Dwibedi V, Kalia S, Saxena S (2019) Isolation and enhancement of resveratrol production in Xylaria psidii by exploring the phenomenon of epigenetics: using DNA methyltransferases and histone deacetylase as epigenetic modifiers. Mol Biol Rep 46:4123–4137. https://doi.org/10.1007/s11033-019-04862-z
Félix C, Salvatore MM, DellaGreca M et al (2019) Secondary metabolites produced by grapevine strains of Lasiodiplodia theobromae grown at two different temperatures. Mycologia 111:466–476. https://doi.org/10.1080/00275514.2019.1600342
Gharbi I, Issaoui M, Gharbi SE et al (2017) Butylated hydroxytoluene (BHT) emitted by fungi naturally occurring in olives during their pre-processing storage for improving olive oil stability. Eur J Lipid Sci Technol 119:1600343. https://doi.org/10.1002/ejlt.201600343
González-Menéndez V, Pérez-Bonilla M, Pérez-Victoria I et al (2016) Multicomponent analysis of the differential induction of secondary metabolite profiles in fungal endophytes. Molecules 21:234. https://doi.org/10.3390/molecules21020234
Gupta P, Yadav DK, Siripurapu KB, Palit G et al (2007) Constituents of Ocimum sanctum with antistress activity. J Nat Prod 70:1410–1416. https://doi.org/10.1021/np0700164
Kitagawa I, Hayashi K, Kobayashi M (1989) Heterosigma-glycolipids I and II, two new galactolipids containing octadecatetraenoyl and eicosapentaenoyl residues, from a raphidophyte dinoflagellate Heterosigma sp. Chem Pharm Bull 37:849–851. https://doi.org/10.1248/cpb.37.849
Kokubo T, Taniguchi Y, Kanayama M et al (2011) Extract of the mushroom Mycoleptodonoides aitchisonii induces a series of anti-oxidative and phase II detoxifying enzymes through activation of the transcription factor Nrf2. Food Chem 129:92–99. https://doi.org/10.1016/j.foodchem.2011.04.031
Kudalkar P, Strobel G, Riyaz-Ul-Hassan S et al (2012) Muscodor sutura, a novel endophytic fungus with volatile antibiotic activities. Mycoscience 1:319–325. https://doi.org/10.1007/S10267-011-0165-9
Magotra A, Kumar M, Kushwaha M et al (2017) Epigenetic modifier induced enhancement of fumiquinazoline C production in Aspergillus fumigatus (GA-L7): an endophytic fungus from Grewia asiatica L. AMB Express 7:43. https://doi.org/10.1186/s13568-017-0343-z
Martínez-Soto D, Ortiz-Castellanos L, Robledo-Briones M et al (2020) Molecular mechanisms involved in the multicellular growth of Ustilaginomycetes. Microorganisms 8:1072. https://doi.org/10.3390/microorganisms8071072
Pan R, Bai X, Chen J, Zhang H, Wang H (2019) Exploring structural diversity of microbe secondary metabolites using OSMAC strategy: a literature review. Front. Microbiol. 10:294. https://doi.org/10.3389/fmicb.2019.00294
Pfannenstiel BT, Keller NP (2019) On top of biosynthetic gene clusters: how epigenetic machinery influences secondary metabolism in fungi. Biotechnol Adv 37:107345. https://doi.org/10.1016/j.biotechadv.2019.02.001
Poolchanuan P, Unagul P, Thongnest S et al (2020) An anticonvulsive drug, valproic acid (valproate), has effects on the biosynthesis of fatty acids and polyketides in microorganisms. Sci Rep 10:9300. https://doi.org/10.1038/s41598-020-66251-y
Sharma V, Singamaneni V, Sharma N et al (2018) Valproic acid induces three novel cytotoxic secondary metabolites in Diaporthe sp., an endophytic fungus from Datura inoxia Mill. Bioorg Med Chem Lett 28:2217–2221. https://doi.org/10.1016/j.bmcl.2018.04.018
Singh G, Katoch A, Razak M et al (2017) Bioactive and biocontrol potential of endophytic fungi associated with Brugmansia aurea Lagerh. FEMS Microbiol Lett 364:fnx194. https://doi.org/10.1093/femsle/fnx194
Singh G, Singh J, Singamaneni V et al (2021) Serine-glycine-betaine, a novel dipeptide from an endophyte Macrophomina phaseolina: isolation, bioactivity and biosynthesis. J Appl Microbiol 131:756–767. https://doi.org/10.1111/jam.14995
Stierle AA, Stierle DB (2015) Bioactive secondary metabolites produced by the fungal endophytes of conifers. Nat Prod Commun 10:1671–1682. https://doi.org/10.1177/1934578X1501001012
Strobel G, Daisy B (2003) Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 67:491–502. https://doi.org/10.1128/MMBR.67.4.491-502.2003
Suresh JI, Sona N (2021) Fungal endophytes, biodiversity and biopotential applications. Fungi Bio-Prospects in Sustainable Agriculture, Environment and Nano-Technology, Academic Press 1:107–115. https://doi.org/10.1016/B978-0-12-821394-0.00005-6
Wei J, Chen F, Liu Y et al (2020) Comparative metabolomics revealed the potential antitumor characteristics of four endophytic fungi of Brassica rapa L. ACS Omega 5:5939–5950. https://doi.org/10.1021/acsomega.9b04258
Yang X-L, Awakawa T, Wakimoto T, Abe I (2013) Induced biosyntheses of a novel butyrophenone and two aromatic polyketides in the plant pathogen Stagonospora nodorum. Nat Prod Bioprospecting 3:141–144. https://doi.org/10.1007/s13659-013-0055-2
Ye B, Wu Y, Zhai X et al (2020) Beneficial effects of endophytic fungi from the anoectochilus and ludisia species on the growth and secondary metabolism of anoectochilus roxburghii. ACS Omega 5:3487–3497. https://doi.org/10.1021/acsomega.9b03789
Ying Y-M, Li L, Yu H-F et al (2020) Induced production of a new polyketide in Penicillium sp. HS-11 by chemical epigenetic manipulation. Nat Prod Res 35:1446–1451. https://doi.org/10.1080/14786419.2019.1709190
Yu H, Zhang L, Li L et al (2010) Recent developments and future prospects of antimicrobial metabolites produced by endophytes. Microbiol Res 165:437–449. https://doi.org/10.1016/j.micres.2009.11.009
Zheng CJ, Xu LL, Li YY et al (2013) Cytotoxic metabolites from the cultures of endophytic fungi from Panax ginseng. Appl Microbiol Biotechnol 97:7617–7625. https://doi.org/10.1007/s00253-013-5015-6
Acknowledgements
We thankfully acknowledge the Council of Scientific and Industrial Research (CSIR) for providing the platform for research. MK acknowledges the DBT, Govt. of India, for financial assistance (BT/PR4669/PBD/17/784/2012), while GS acknowledges the ICMR for the SRFship (ISRM/11(76)/2017). The manuscript bears IIIM Communication No. CSIR-IIIM/IPR/00360.
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Singh, G., Kumar, A., Verma, M.K. et al. Secondary metabolites produced by Macrophomina phaseolina, a fungal root endophyte of Brugmansia aurea, using classical and epigenetic manipulation approach. Folia Microbiol 67, 793–799 (2022). https://doi.org/10.1007/s12223-022-00976-3
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DOI: https://doi.org/10.1007/s12223-022-00976-3