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The trypsin inhibitors have various role in diseases such as inflammation, Alzheimer's disease, pancreatitis, rheumatoid arthritis, cancer prognosis, metastasis and so forth. From 10 endophytic fungi isolated, we were able to screen only one strain with the required activity. The fungus with activity was obtained as an endophyte from <jats:italic>Dendrophthoe falcata<\/jats:italic> and was later identified as <jats:italic>Nigrospora sphaerica<\/jats:italic>. The activity was checked by enzyme assays using trypsin. The fungus was fermented and the metabolites were extracted and further purified by bioassay\u2010guided chromatographic methods and the compound isolated was identified using gas chromatography\u2013mass spectrometry. The compound was identified as quercetin. Docking studies were employed to study the interaction. The absorption, distribution, metabolism, and excretion analysis showed satisfactory results and the compound has no AMES and hepatotoxicity. This study reveals the ability of <jats:italic>N. sphaerica<\/jats:italic> to produce bioactive compound quercetin has been identified as a potential candidate for trypsin inhibition. The present communication describes the first report claiming that <jats:italic>N. sphaerica<\/jats:italic> strain AVA\u20101 can produce quercetin and it can be considered as a sustainable source of trypsin active\u2010site inhibitors.<\/jats:p>","DOI":"10.1002\/jobm.202100221","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T13:34:25Z","timestamp":1625578465000},"page":"709-720","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of sustainable trypsin active\u2010site inhibitors from <i>Nigrospora sphaerica<\/i> strain AVA\u20101"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9613-3259","authenticated-orcid":false,"given":"Anoop","family":"Kallingal","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Microbiology, School of Life Science Kannur University Palayad Kerala India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4797-8850","authenticated-orcid":false,"given":"Varun","family":"Thachan Kundil","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Microbiology, School of Life Science Kannur University Palayad Kerala India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-1703","authenticated-orcid":false,"given":"Aravind","family":"Ayyolath","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Microbiology, School of Life Science Kannur University Palayad Kerala India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-5834","authenticated-orcid":false,"given":"Tomy","family":"Muringayil Joseph","sequence":"additional","affiliation":[{"name":"Polymers Technology Department, Chemical Faculty Gdansk University of Technology Gdansk Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3986-0337","authenticated-orcid":false,"given":"Debarshi","family":"Kar Mahapatra","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Dadasaheb Balpande College of Pharmacy Nagpur Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6377-7050","authenticated-orcid":false,"given":"J\u00f3zef T.","family":"Haponiuk","sequence":"additional","affiliation":[{"name":"Polymers Technology Department, Chemical Faculty Gdansk University of Technology Gdansk Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1450-2648","authenticated-orcid":false,"given":"E. 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