title: Cysteine Protease Inhibitors Produced by the Industrial Koji Mold, Aspergillus oryzae O-1018.
abstract: Aspergillus oryzae O-1018 (FERM P-15834) separated from industrial koji for brewing sake was found to produce five papain-inhibitory compounds in the culture supernatant. The five isolated inhibitors were named CPI-1 to CPI-5, and their structures were elucidated by spectroscopic analyses and chemical degradation. We determined the structures of CPI-2, CPI-3 and CPI-4 as 4-amino-1-[[N- [(2S, 3S)-3-trans-carboxyoxiran-2-carbonyl]-L-isoleucyl] amino]butane, 5-amino-1-[[N-[(2S, 3S)-3-trans-carboxyoxiran-2-carbonyl]-L-isoleucyl]amino]pentane and N (8)- [N-[(2S, 3S)-3-trans-carboxyoxiran-2-carbonyl]-L-isoleu-cyl]spermidine, respectively. We also confirmed by a degradation experiment that CPI-1 consisted of L-trans-epoxysuccinic acid, L-tyrosine and spermidine, and that CPI-5 was composed of L-trans-epoxysuccinic acid, L-phenylalanine and spermidine. Although CPI-4 was identified as kojistatin A,(1)) the other CPIs seemed to be novel compounds. All CPIs were cysteine protease-specific inhibitors with appreciable selectivity toward cathepsin B and L. The inhibition potency of CPIs against cysteine proteases was as high as or higher than that of E-64. In particular, CPI-2, -3 and -4 were ten times more effective than E-64 toward cathepsin B and L, and CPI-1 and -5 were about 100 times more inhibitory than E-64 toward cathepsin L.
authors.affiliation: a Research Institute, Gekkeikan Sake Co. Ltd.
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.affiliation: b Institute for Chemical Research, Kyoto University.
authors.forename: J
authors.initials: J
authors.lastname: Hiratake
authors.affiliation: a Research Institute, Gekkeikan Sake Co. Ltd.
authors.forename: M
authors.initials: M
authors.lastname: Aikawa
authors.affiliation: a Research Institute, Gekkeikan Sake Co. Ltd.
authors.forename: T
authors.initials: T
authors.lastname: Suizu
authors.affiliation: a Research Institute, Gekkeikan Sake Co. Ltd.
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.affiliation: a Research Institute, Gekkeikan Sake Co. Ltd.
authors.forename: A
authors.initials: A
authors.lastname: Kawato
authors.affiliation: a Research Institute, Gekkeikan Sake Co. Ltd.
authors.forename: K
authors.initials: K
authors.lastname: Suginami
authors.affiliation: b Institute for Chemical Research, Kyoto University.
authors.forename: J
authors.initials: J
authors.lastname: Oda
keywords: Aspergillus oryzae; cysteine protease inhibitor; koji mold; trans-epoxysuccinyl derivative