We identified a novel fermented substance (FKA) produced by the edible Aspergillus oryzae strain AO-1 that inhibited dipeptidyl peptidase IV (DPP-IV) (IC50 = 3.41 mg . mL(-1))" HPLC analysis of FKA showed specific one metabolite (WYK-1), which inhibited DPP-IV (IC50 = 6.98 mu M). WYK-1 was identified as a tetrahydroxyisoquinoline derivative. Interestingly, we examined 60 strains of A. oryzae, AO-1 was the only A. oryzae strain that produces WYK-1. This is the first report that an edible A. oryzae strain produces a DPP-IV inhibitor such as WYK-1. This study also suggests that FKA has applications in the development of novel antihyperglycemic therapeutics or functional foods. (C) 2010, The Society for Biotechnology, Japan. All rights reserved.