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Application of Bioassay-Guided Fractionation Coupled with a Molecular Approach for the Dereplication of Antimicrobial Metabolites

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Abstract

A systematically delineated dereplication approach was described based on genome mining and bioassay-guided fractionation using endophytic fungus Xylaria psidii FPL-52(S) isolated from leaves of Ficus pumila Linn., (Moraceae). A polyketide synthase gene-based molecular screening strategy by a degenerate oligonucleotide primer polymerase chain reaction technique coupled with a bioinformatic phylogenomic approach revealed the presence of an iterative polyketide synthase gene within the genome of Xylaria psidii FPL-52(S). Chemical dereplication of ethyl acetate extract derived from a submerged fermentation culture broth of Xylaria psidii FPL-52(S) by bioassay-guided chromatographic and hyphenated analytical spectroscopic techniques led to the identification of polyketide mycoalexin 3-O-methylmellein. Antimicrobial profiling and minimal inhibitory concentration values for 3-O-methylmellein were determined by disc diffusion and microbroth dilution techniques. Gram-positive bacteria, dermatophytic and phytopathogenic fungi were susceptible in terms of inhibition zone and minimum inhibitory concentration values when compared to co-assayed standards. Herein, we highlight and demonstrate an improved approach which facilitates efficient dereplication and effect-guided fractionation of antimicrobial metabolite(s). The present work flow serves as a promising dereplication tool to survey the biosynthetic potential of endophytic fungal diversity, thereby identifying the most promising strains and prioritizing them for novel polyketide-derived antimicrobial metabolite discovery.

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Acknowledgements

Funding was provided by the University Grants Commission (Grant No. 37-449/2009), Department of Science and Technology (DST-SERB), New Delhi, India. We gratefully acknowledge the help of Prof. Dr. Marc Stadler, Head of research department ‘Microbial Drugs’, Dr. Eric Kuhnert, post doctoral fellow and Pia Philine Wotsch, Technical assistant, Helmholtz Centre for Infection Research, Braunschweig, Germany, during our molecular identification of mycoendo-symbiotic Xylaria psidii-FPL-52(S). We also gratefully acknowledge the kind help of Dr. Fernando Reyes, Head of the Chemistry Department at Fundacin Medina, Spain (PHARMASEA) for structure elucidation. We also acknowledge Dr. Shrisha, D. L., and Dr. Nagabhushan for their help in collection and identification of host Ficus pumila Linn., (Moraceae). We sincerely acknowledge Spectroscopy/Analytical Test Facility (SATF), Society for Innovation and Development (SID), Indian Institute of Science (IISc), Bangalore, Karnataka, India for LC-MS analytical facility. We also thanks technical staffs of Vijnana Bhavan, IOE and UGC-PURSE, MHRD (UGC) Government of India, University of Mysore, Mysore, Karnataka, India, for providing NMR and FT-IR instrumentation facilities.

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Authors and Affiliations

  1. Microbial Drugs Laboratory, Department of Studies in Microbiology, Manasagangotri, University of Mysore, Mysore, 570 006, Karnataka, India

    Devaraju Rakshith, H. C. Yashavantha Rao, Azmath Pasha & Sreedharamurthy Satish

  2. National Bureau of Agricultural Insect Resources, P. Bag No: 2491, H.A. Farm Post, Bellary Road, Bengaluru, 560 024, Karnataka, India

    Parthasarathy Santosh

  3. Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, 247 667, Uttarakhand, India

    T. P. Pradeep

  4. Post Graduate Department of Chemistry, Sarada Vilas College, Mysore, 570 004, Karnataka, India

    Doddahosuru Mahadevappa Gurudatt

  5. Laboratory of Biotechnology of New Materials in Siberian Federal University, Krasnoyarsk, Russia

    Syed Baker

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  1. Devaraju Rakshith
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  2. Parthasarathy Santosh
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  3. T. P. Pradeep
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  8. Sreedharamurthy Satish
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Rakshith, D., Santosh, P., Pradeep, T.P. et al. Application of Bioassay-Guided Fractionation Coupled with a Molecular Approach for the Dereplication of Antimicrobial Metabolites. Chromatographia 79, 1625–1642 (2016). https://doi.org/10.1007/s10337-016-3188-8

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