title: Inhibitory effect of aflastatin A on melanin biosynthesis by Colletotrichum lagenarium.
abstract: The effect of aflastatin A (AsA), a novel inhibitor of aflatoxin production, on melanin biosynthesis of Colletotrichum lagenarium was examined. Addition of a low concentration of AsA (0.5 microg ml(-1)) to the culture medium almost completely inhibited the melanin production of this organism. AsA also inhibited the production of scytalone, an early intermediate of melanin biosynthesis. Melanin production was restored by addition of exogenous scytalone in the presence of AsA, suggesting that the late steps after the synthesis of scytalone were not significantly affected by AsA. This was confirmed by the results from RT-PCR analysis of the expression of genes encoding melanin biosynthetic enzymes (SCD1, THR1) and a regulatory gene (CMR1). By contrast, expression of PKS1 was severely impaired by AsA, although catalytic activity of a polyketide synthase (PKS1) was not inhibited by AsA. These results indicate that AsA inhibits an early step in melanin production, which suppresses the expression of PKS1.
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan1.
authors.forename: Susumu
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan1.
authors.forename: Masaru
authors.initials: M
authors.lastname: Sakurada
authors.affiliation: Faculty of Agriculture, Kyoto Prefectural University, Shimogamo, Kyoto 606-8522, Japan2.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Faculty of Agriculture, Kyoto Prefectural University, Shimogamo, Kyoto 606-8522, Japan2.
authors.forename: Gento
authors.initials: G
authors.lastname: Tsuji
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan3.
authors.forename: Isao
authors.initials: I
authors.lastname: Fujii
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan3.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ebizuka
authors.affiliation: Morinaga and Co., Ltd, Tsurumi-ku, Yokohama 230-8504, Japan4.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan1.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Nagasawa
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan1.
authors.forename: Shohei
authors.initials: S
authors.lastname: Sakuda
mesh_terms: D001483:Base Sequence; D020231:Colletotrichum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005800:Genes, Fungal; D008543:Melanins / Q000096:biosynthesis*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009284:Naphthols / Q000378:metabolism / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*
chemical_list: D004271:DNA, Fungal; D008543:Melanins; D009097:Multienzyme Complexes; D009284:Naphthols; D011760:Pyrrolidinones; C105377:aflastatin A; C012547:scytolone