Blasticidin A Derivatives with Highly Specific Inhibitory Activity toward Aflatoxin Production in Aspergillus parasiticus.

Sakuda, Shohei; Ikeda, Hiroyuki; Nakamura, Takefumi; Kawachi, Ryu; Kondo, Toshiyuki; Ono, Masafumi; Sakurada, Masaru; Inagaki, Hideaki; Ito, Ryouichi; Nagasawa, Hiromichi

doi:10.7164/antibiotics.53.1378

Cited by 28 publications

(19 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A small amount of aflatoxin (less than 3 % of the total amount in the culture broth) was obtained from the mycelium of the fungus in the control culture, but aflatoxin was not detected in the mycelium cultured in the presence of DotA at a concentration of 0.2 mM, indicating that DotA inhibited aflatoxin production without causing accumulation of aflatoxin in the mycelium. Unlike AsA and BcA, DotA showed no antibiotic activity toward S. cerevisiae at a concentration of 50 mM (data not shown) (Sakuda et al, 2000b).…”

Section: Resultsmentioning

confidence: 91%

See 1 more Smart Citation

Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus

et al. 2007

Self Cite

View full text Add to dashboard Cite

Dioctatin A (DotA), a metabolite of Streptomyces, is known to be an inhibitor of human dipeptidyl aminopeptidase II. Here, it was found that DotA strongly inhibited aflatoxin production by Aspergillus parasiticus, with an IC 50 value of 4.0 mM. The mycelial growth of the fungus was not affected by the addition of DotA at a concentration of 50 mM, but inhibition of conidiation was observed at the same concentration. DotA inhibited production of norsolorinic acid, an early biosynthetic intermediate of aflatoxin, and it strongly reduced the mRNA levels of genes encoding aflatoxin biosynthetic enzymes, and significantly decreased the mRNA level of aflR, which encodes a key regulatory protein for aflatoxin biosynthesis. In addition to these genes, the mRNA level of brlA, which encodes a conidiation-specific transcription factor, was also reduced by the addition of DotA. It was also found that DotA dramatically enhanced kojic acid production by the fungus. Furthermore, DotA inhibited production of sterigmatocystin, which is a toxic aflatoxin biosynthetic intermediate, and it also inhibited conidiation in Aspergillus nidulans. These results indicate that DotA has pleiotropic effects on regulatory mechanisms of fungal secondary metabolite production and differentiation, leading to inhibition of aflatoxin production.

show abstract

Section: Resultsmentioning

confidence: 91%

“…BcA has antibiotic activity toward the yeast Saccharomyces cerevisiae (Sakuda et al, 2000b). During the course of a recent investigation into the mode of action of BcA in the yeast, we observed that the amount of a diketopiperazine produced in yeast cells was drastically reduced in the presence of BcA (unpublished data).…”

Section: Introductionmentioning

confidence: 88%

Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…BcA showed antimicrobial activity toward Saccharomyces cerevisiae. 10 Our attempt to obtain BcA-resistant strains by transformation of S. cerevisiae with cDNA or genomic libraries has not afforded critical candidate genes for investigating a target molecule (data not shown). Therefore, analysis of the yeast proteome by two-dimensional differential gel electrophoresis (2D-DIGE) 11 was performed.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory activity of blasticidin A, a strong aflatoxin production inhibitor, on protein synthesis of yeast: selective inhibition of aflatoxin production by protein synthesis inhibitors

et al. 2010

Self Cite

View full text Add to dashboard Cite

Blasticidin A (BcA), an antibiotic produced by Streptomyces, inhibits aflatoxin production without strong growth inhibition toward aflatoxin-producing fungi. During the course of our study on the mode of action of BcA by two-dimensional differential gel electrophoresis (2D-DIGE), we found a decrease in the abundances of ribosomal proteins in Saccharomyces cerevisiae after exposure to BcA. This phenomenon was also observed by treatment with blasticidin S (BcS) or cycloheximide. BcA inhibited protein synthesis in a galactose-induced expression system in S. cerevisiae similar to BcS and cycloheximide. BcS, but not cycloheximide, inhibited aflatoxin production in Aspergillus parasiticus without inhibition of fungal growth, similar to BcA. A decrease in the abundances of aflatoxin biosynthetic enzymes was observed in 2D-DIGE experiments with Aspergillus flavus after exposure to BcA or BcS. These results suggested that protein synthesis inhibitors are useful to control aflatoxin production.

show abstract

“…Streptomyces are soil-borne bacteria that can develop in crops and that are known to be good biocontrol candidates (Bressan & Figueiredo, 2008). Studies have shown that Streptomyces metabolites are sources of AF repressors (Ono et al, 1997;Sakuda et al, 2000). However, until recently no studies have focused on Streptomyces-Aspergillus mutual interactions and their impact on AF production and AF gene expression.…”

Section: Introductionmentioning

confidence: 99%

Reduction of aflatoxin production by Aspergillus flavus and Aspergillus parasiticus in interaction with Streptomyces

et al. 2015

View full text Add to dashboard Cite

The aim of this study is to investigate aflatoxin gene expression during Streptomyces-Aspergillus interaction. Aflatoxins are carcinogenic compounds produced mainly by Aspergillus flavus and Aspergillus parasiticus. A previous study has shown that Streptomyces-A. flavus interaction can reduce aflatoxin content in vitro. Here, we first validated this same effect in the interaction with A. parasiticus. Moreover, we showed that growth reduction and aflatoxin content were correlated in A. parasiticus but not in A. flavus. Secondly, we investigated the mechanisms of action by reversetranscriptase quantitative PCR. As microbial interaction can lead to variations in expression of household genes, the most stable [act1, btub (and cox5 for A. parasiticus)] were chosen using geNorm software. To shed light on the mechanisms involved, we studied during the interaction the expression of five genes (aflD, aflM, aflP, aflR and aflS). Overall, the results of aflatoxin gene expression showed that Streptomyces repressed gene expression to a greater level in A. parasiticus than in A. flavus. Expression of aflR and aflS was generally repressed in both Aspergillus species. Expression of aflM was repressed and was correlated with aflatoxin B1 content. The results suggest that aflM expression could be a potential aflatoxin indicator in Streptomyces species interactions. Therefore, we demonstrate that Streptomyces can reduce aflatoxin production by both Aspergillus species and that this effect can be correlated with the repression of aflM expression. INTRODUCTIONAflatoxins (AFs) are polyketide-derived furanocoumarins. They are produced by fungi of the genus Aspergillus (including Aspergillus flavus and Aspergillus parasiticus) in agricultural foodstuffs (maize, hazelnut, peanut, etc.) (Giorni et al., 2007;Passone et al., 2010). These AFs are toxic and their main adverse effects on humans are hepatocarcinoma (Qian et al., 1994; IARC, 2014), immune system deficiency (Jiang et al., 2005), reduced child growth (Gong et al., 2004) and increased risks of stillborn or newborn jaundice (Shuaib et al., 2010). To reduce those multiple effects, many countries have implemented maximum authorized levels of AFs in food and feed (Wu & Guclu, 2012). AF biosynthesis is coded by a 80 kb long DNA sequence. The latter is a cluster containing 30 putative genes characterized in both A. flavus and A. parasiticus (Yu, 2012). For structural genes, early (as aflD), medium (as aflM) and late (as aflP) genes are denominated (Fig. S1, available in the online Supplementary Material). The gene aflD encodes a reductase enzyme involved in the conversion of norsolorinic acid to averantin (Papa, 1982); aflM is required for the conversion of versicolorin A to demethylsterigmatocystin (Skory et al., 1992); and aflP encodes a methyltransferase converting sterigmatocystin to O-methylsterigmatocystin (Bhatnagar et al., 1988). Two cluster-specific regulators are also known: aflR encodes a transcription activator that binds a consensus sequence in the promoter regions of AF ...

show abstract

Blasticidin A Derivatives with Highly Specific Inhibitory Activity toward Aflatoxin Production in Aspergillus parasiticus.

Cited by 28 publications

References 11 publications

Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus

Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus

Inhibitory activity of blasticidin A, a strong aflatoxin production inhibitor, on protein synthesis of yeast: selective inhibition of aflatoxin production by protein synthesis inhibitors

Reduction of aflatoxin production by Aspergillus flavus and Aspergillus parasiticus in interaction with Streptomyces

Contact Info

Product

Resources

About