Blasticidin A derivatives with highly specific inhibitory activity toward aflatoxin production in Aspergillus parasiticus.
Blasticidin A (1), an antibiotic, has strong inhibitory activity toward aflatoxin production by Aspergillus parasiticus. We prepared some derivatives of 1 and examined their biological activities. Among them, derivatives 3 and 4 without the tetramic acid moiety of 1 maintained inhibitory activity toward aflatoxin production, but did not show antifungal activity or toxicity. RT-PCR experiments indicated that derivatives 3 and 4 as well as 1 significantly reduced the expression of genes encoding aflatoxin biosynthetic enzymes (pksA, ver-1 and omtA) and a regulatory gene (aflR) in A. parasiticus. These results suggested that derivatives 3 and 4 can inhibit aflatoxin production more specifically than 1 by inhibiting an early step prior to the expression of aflR in the pathway of aflatoxin biosynthesis.
Sakuda
S
S
Department of Applied Biological Chemistry, The University of Tokyo, Japan.
Ikeda
H
H
Nakamura
T
T
Kawachi
R
R
Kondo
T
T
Ono
M
M
Sakurada
M
M
Inagaki
H
H
Ito
R
R
Nagasawa
H
H
D000348:Aflatoxins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects* / Q000378:metabolism; D001483:Base Sequence; D017931:DNA Primers; D015394:Molecular Structure; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000348:Aflatoxins; D000900:Anti-Bacterial Agents; D017931:DNA Primers; D011760:Pyrrolidinones; C420726:blasticidin A