Open AccessNovel Antifungal Compound Z-705 Specifically Inhibits Protein Kinase C of Filamentous Fungi
Author(s) -
Asumi Sugahara,
Akira Yoshimi,
Fumio Shoji,
Tomonori Fujioka,
Kiyohiko Kawai,
Hideaki Umeyama,
Katsuichiro Komatsu,
Masaru Enomoto,
Shigefumi Kuwahara,
Daisuke Hagiwara,
Takuya Katayama,
Hiroyuki Horiuchi,
Ken Miyazawa,
Mayumi Nakayama,
Keietsu Abe
Publication year - 2019
Publication title -
applied and environmental microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.552
H-Index - 324
eISSN - 1070-6291
pISSN - 0099-2240
DOI - 10.1128/aem.02923-18
Subject(s) - staurosporine , protein kinase c , magnaporthe grisea , microbiology and biotechnology , biology , protein kinase a , saccharomyces cerevisiae , kinase , hypha , fungal protein , biochemistry , yeast , oryza sativa , gene
A candidate inhibitor of filamentous fungal protein kinase C (PKC), Z-705, was identified byin silico screening. A screening system to evaluate the effects of fungal PKC inhibitors was constructed inSaccharomyces cerevisiae . Using this system, we found that Z-705 is highly selective for filamentous fungal PKC in comparison withS. cerevisiae PKC. Analysis of theAGS1 mRNA level, which is regulated by Mps1p mitogen-activated protein kinase (MAPK) via PKC, in the rice blast fungusMagnaporthe grisea revealed that Z-705 had a PKC inhibitory effect comparable to that of staurosporine. Micafungin induced hyphal melanization inM. grisea , and this melanization, which is required for pathogenicity ofM. grisea , was inhibited by PKC inhibition by both Z-705 and staurosporine. The mRNA levels of4HNR ,3HNR , andSCD1 , which are essential for melanization inM. grisea , were suppressed by both PKC inhibitors.
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