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Stimulation of secondary metabolite production in Hypoxylon anthochroum by naturally occurring epigenetic modifiers

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Abstract

In pursuit of discovering novel compounds of pharmacological significance, plants and microbes are the potential sources. Endophytic fungi are well-known producers of a myriad class of bioactive metabolites but in laboratory conditions, a substantial number of biosynthetic pathways remain quiescent or under-expressed in conventional culture conditions. Hence, major potential of them is neglected during regular fermentation process. Epigenetic modifiers are reported to modulate fungal genome by altering the expression of metabolite production. Our present study evidences the induction of cryptic secondary metabolite production by Hypoxylon anthochroum, a foliar endophytic fungus of Carica papaya when treated with extracts of garlic and curry leaves. Garlic (Allium sativum), produces allyl mercaptan and diallyl disulfide as the major constituents of organosulfur compounds, which are known to act as inhibitors of histone deacetylases (HDAC). Similarly, Curry leaves (Murraya koenigii) produce mahanine, a carbazole alkaloid, causes DNA methyltransferase (DNMT) inhibition. Hypoxylon anthochroum, when treated with extract of garlic and curry leaves, resulted in 416.12 and 333.33% increase in yield of secondary metabolites, 89% and 85% increase in antioxidant property respectively, along with enhanced antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. High-performance liquid chromatography analysis of the crude extract of H. anthochroum revealed the induction of 19 and 10 new compounds when treated with garlic and curry leaf extracts, respectively, when compared to untreated control. This study suggests that treatment with HDAC inhibitor in the form of garlic extract was more effective than treatment with DNMT inhibitor in curry leaf extract in inducing cryptic metabolites.

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Abbreviations

DNMT:

DNA methyltransferase

HDAC:

Histone deacetylase

HPLC:

High performance liquid chromatography

CWT:

Control without treatment

CLT:

Curry leaf treatment

GRT:

Garlic treatment

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Acknowledgments

Authors thank the Department of Biotechnology, Pondicherry University, 605014, Puducherry, India, for providing all the facilities. RM thanks CSIR for fellowship, JSK thanks Pondicherry University for fellowship. We also thank UGC-SAP, Govt. of India and DST-FIST, Govt. of India for infrastructural support.

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This work has not been funded by any agency or source.

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Authors and Affiliations

  1. Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India

    Rashmi Mishra, Jai Shanti Kushveer, Debashis Majumder & Vemuri Venkateswara Sarma

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  1. Rashmi Mishra
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  2. Jai Shanti Kushveer
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  3. Debashis Majumder
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  4. Vemuri Venkateswara Sarma
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Contributions

RM and JSK equally contributed to the study. Experimental design and concept by RM. Experiments performed by RM, JSK, DM. Manuscript writing by RM, JSK. Overall supervision, manuscript evaluation and correction by VVS.

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Correspondence to Vemuri Venkateswara Sarma.

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Mishra, R., Kushveer, J.S., Majumder, D. et al. Stimulation of secondary metabolite production in Hypoxylon anthochroum by naturally occurring epigenetic modifiers. Food Measure 14, 946–962 (2020). https://doi.org/10.1007/s11694-019-00345-8

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