Inhibitory effect of aflastatin A on melanin biosynthesis by Colletotrichum lagenarium.
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.
Okamoto
Susumu
S
Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan1.
Sakurada
Masaru
M
Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan1.
Kubo
Yasuyuki
Y
Faculty of Agriculture, Kyoto Prefectural University, Shimogamo, Kyoto 606-8522, Japan2.
Tsuji
Gento
G
Faculty of Agriculture, Kyoto Prefectural University, Shimogamo, Kyoto 606-8522, Japan2.
Fujii
Isao
I
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan3.
Ebizuka
Yutaka
Y
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan3.
Ono
Makoto
M
Morinaga and Co., Ltd, Tsurumi-ku, Yokohama 230-8504, Japan4.
Nagasawa
Hiromichi
H
Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan1.
Sakuda
Shohei
S
Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan1.
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*
D004271:DNA, Fungal; D008543:Melanins; D009097:Multienzyme Complexes; D009284:Naphthols; D011760:Pyrrolidinones; C105377:aflastatin A; C012547:scytolone