ORIGINAL ARTICLE Antidiabetic potential of a peptide isolated from an endophytic Aspergillus awamori B. Singh and A. Kaur Department of Microbiology, Guru Nanak Dev University, Amritsar, India Keywords antidiabetic, Aspergillus awamori, bioactive peptide, endophytic fungi, glycosidase inhibitor. Correspondence Amarjeet Kaur, Department of Microbiology, Guru Nanak Dev University, Amritsar 143005 Punjab, India. E-mail: amarjeet_b@rediffmail.com 2015/1559: received 5 June 2015, revised 24 September 2015 and accepted 17 October 2015 doi:10.1111/jam.12998 Abstract Aim: To exploit the potential of endophytic fungi for pharmaceutically important antidiabetic alpha glycosidase inhibitors. Methods and Results: Thirty six endophytic fungi were isolated from Acacia nilotica and screened for the production of alpha amylase and glucosidase inhibitors. Inhibitory activity against both alpha amylase (81%) and alpha glucosidase (80%) was exhibited in an isolate, identified to be Aspergillus awamori. Purification of the inhibitor was carried out on Sephadex LH-20 column and semi prep HPLC. The inhibitor was characterized to be proteinaceous in nature with an approximate molecular mass of 22 kDa. UHPLC amino acid analysis indicated the presence of amino acids serine, threonine, tyrosine and valine in the peptide. The purified inhibitor exhibited mixed type of inhibition against alpha amylase and alpha glucosidase with IC 50 values of 3Á75 and 5Á625 lg ml À1 respectively. The inhibitor was stable over a wide range of pH and temperature. Optimization of process parameters to increase the yield of the inhibitor was undertaken using one factor at a time approach as well as RSM statistical analysis. The interaction of dextrose and proteose peptone for the test organism was significant with first order effect of pH. Increase of 13% was obtained in the inhibitory activity after optimization of process parameters. Mutagenicity testing by Ames test revealed nonmutagenic nature of the peptide. Conclusion: Endophytic A. awamori is capable of producing a peptide with alpha glycosidase inhibitory activity. Significance and Impact of the Study: The inhibitor obtained in this study possesses dual (alpha glucosidase and alpha amylase) inhibitory activity, low IC 50 values, is highly stable under extreme conditions of pH and temperature, and is nonmutagenic in nature. By virtue of its properties it can be commercially produced and exploited for better management of diabetes. Introduction Diabetes mellitus (DM) is the most common endocrine disease worldwide with number of people suffering from this disease expected to reach 366 million by 2030 (Funke and Melzig 2006). DM type 2, a noninsulin-dependent type of diabetes is the most common type of DM, with 90–95% of people suffering from this type of disease. The increasing trend in type 2 DM has become a serious medical concern worldwide necessitating the exploration for new therapeutic agents. The most challenging goal in management of patients with DM is to achieve blood glu- cose level as close to normal. The control of kinetics of carbohydrate hydrolyzing enzymes and monosaccharide absorption could be valuable in the prevention and con- trol of DM (Alagesan et al. 2012). Alpha-glucosidase and alpha amylase are the important enzymes responsible for the hydrolysis of complex dietary saccharides and monosaccharides to glucose in the digestive system. The mucosal alpha glucosidases act synergistically with pan- creatic alpha amylase to digest granular starch (Dhital et al. 2013). On administering glycosidase inhibitors with carbohydrates, they compete with the binding of starch and oligosaccharides thereby slowing the digestion pro- Journal of Applied Microbiology 120, 301--311 © 2015 The Society for Applied Microbiology 301 Journal of Applied Microbiology ISSN 1364-5072