Haplofungins, novel inositol phosphorylceramide synthase inhibitors, from Lauriomyces bellulus SANK 26899 I. Taxonomy, fermentation, isolation and biological activities.
In the course of screening for antifungal agents, we have discovered eight novel compounds, haplofungin A, B, C, D, E, F, G and H, from a culture broth of the fungus strain Lauriomyces bellulus SANK 26899. Haplofungins are composed of an arabinonic acid moiety linked through an ester to a modified long alkyl chain and show potent inhibitory activities against fungal inositol phosphorylceramide (IPC) synthase. Haplofungin A inhibited the activity of IPC synthase from Saccharomyces cerevisiae with an IC(50) value of 0.0015 microg ml(-1). This inhibitor also suppressed the growth of Candida glabrata at the MIC value of 0.5 microg ml(-1).
Ohnuki
Takashi
T
Exploratory Research Laboratories I, Daiichi Sankyo Co. Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo, Japan. ohnuki.takashi.eh@daiichisankyo.co.jp
Yano
Tatsuya
T
Ono
Yasunori
Y
Kozuma
Shiho
S
Suzuki
Toshihiro
T
Ogawa
Yasumasa
Y
Takatsu
Toshio
T
D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D001203:Ascomycota / Q000145:classification / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism*; D041221:Candida glabrata / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D005285:Fermentation; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D008826:Microbial Sensitivity Tests; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology; D012988:Soil Microbiology; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006602:Hexosyltransferases; C088714:phosphatidylinositol-ceramide phosphoinositol transferase