Kojic acid biosynthesis in Aspergillus oryzae is regulated by a Zn(II)2Cys6 transcriptional activator and induced by kojic acid at the transcriptional level

Marui, Junichiro; Yamane, Noriko; Ohashi-Kunihiro, Sumiko; Ando, Tomohiro; Terabayashi, Yasunobu; Sano, Motoaki; Ohashi, Satoshi; Ohshima, Eiji; Tachibana, Kuniharu; Higa, Yoshitaka; Nishimura, Mika; Koike, Hideaki; Machida, Masayuki

doi:10.1016/j.jbiosc.2011.03.010

Cited by 74 publications

(68 citation statements)

References 13 publications

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“…Genomic sequencing of A. flavus revealed 55 putative secondary metabolism gene clusters that are differentially regulated through global transcriptional regulators such as LaeA and VeA [2]. Individual secondary metabolic pathways may further be regulated independently by transcriptional regulators located in individual gene clusters for example, aflR and aflS in AF biosynthesis and kojR in kojic acid biosynthesis [2,29,30]. …”

Section: Discussionmentioning

confidence: 99%

The non-metabolizable glucose analog D-glucal inhibits aflatoxin biosynthesis and promotes kojic acid production in Aspergillus flavus

et al. 2014

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BackgroundAflatoxins (AFs) are potent carcinogenic compounds produced by several Aspergillus species, which pose serious threats to human health. As sugar is a preferred carbohydrate source for AF production, we examined the possibility of using sugar analogs to inhibit AF biosynthesis.ResultsWe showed that although D-glucal cannot be utilized by A. flavus as the sole carbohydrate source, it inhibited AF biosynthesis and promoted kojic acid production without affecting mycelial growth when applied to a glucose-containing medium. The inhibition occurred before the production of the first stable intermediate, norsolorinic acid, suggesting a complete inhibition of the AF biosynthetic pathway. Further studies showed that exogenous D-glucal in culture led to reduced accumulation of tricarboxylic acid (TCA) cycle intermediates and reduced glucose consumption, indicating that glycolysis is inhibited. Expression analyses revealed that D-glucal suppressed the expression of AF biosynthetic genes but promoted the expression of kojic acid biosynthetic genes.ConclusionsD-glucal as a non-metabolizable glucose analog inhibits the AF biosynthesis pathway by suppressing the expression of AF biosynthetic genes. The inhibition may occur either directly through interfering with glycolysis, or indirectly through reduced oxidative stresses from kojic acid biosynthesis.

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Section: Discussionmentioning

confidence: 99%

The non-metabolizable glucose analog D-glucal inhibits aflatoxin biosynthesis and promotes kojic acid production in Aspergillus flavus

et al. 2014

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“…The genes are separated by a third gene, which, too, was deleted and found to be behind the formation of the metabolite. 113 The genes encode for an enzyme with an oxidoreductase motif, a transcription factor, and a transporter protein. Glucose, rather than a backbone polyketide, peptide, or terpene, is believed to serve as the starting material.…”

Section: Genetic Characterization Of Other Aspergillus Secondary Mementioning

confidence: 99%

Advances in Aspergillus secondary metabolite research in the post-genomic era

et al. 2012

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This review studies the impact of whole genome sequencing on Aspergillus secondary metabolite research. There has been a proliferation of many new, intriguing discoveries since sequencing data became widely available. What is more, the genomes disclosed the surprising finding that there are many more secondary metabolite biosynthetic pathways than laboratory research had suggested. Activating these pathways has been met with some success, but many more dormant genes remain to be awakened.

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“…A pathway-specific C6-type transcriptional regulator gene present in the ustiloxin B gene cluster (see section 5-6), encoded by ustR, was identified and its overexpression resulted in an increase of ustiloxin B production by about 5-fold while deletion abrogated ustiloxin production 14,17) . Disruption of KA gene cluster (see section 5-8) Zn(2)-Cys(6) transcriptional activator gene, kojR, resulted in a significant down-regulation of expression of KA biosynthetic genes kojA and kojT accompanied by a complete loss of KA production 9) . Over-expression of kojR resulted in >3-fold higher expression of KA biosynthetic genes along with >3-fold increase in KA production compared to the control strain demonstrating direct regulation of KA biosynthesis by KojR.…”

Section: -2 Cluster-specific Regulationmentioning

confidence: 99%

“…Using SMURF, Georgianna et al 8) predicted the genome of A. flavus to contain 55 SM gene clusters. The total number of SM clusters in A. flavus can be increased to 56 when including the kojic acid (KA) gene cluster identified originally in A. oryzae by Marui et al 9) . However this may be an underestimation, as other SM gene cluster prediction programs have identified even greater numbers of gene clusters in A. flavus 10) .…”

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confidence: 99%

<i>Aspergillus flavus</i> Secondary Metabolites: More than Just Aflatoxins

et al. 2018

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Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of these secondary metabolites have been identified from A. flavus cultures, analysis of the genome has predicted the existence of at least 56 secondary metabolite gene clusters. Many of these gene clusters are not expressed during growth of the fungus on standard laboratory media. This presents researchers with a major challenge of devising novel strategies to manipulate the fungus and its genome so as to activate secondary metabolite gene expression and allow identification of associated cluster metabolites. In this review, we discuss the genetic, biochemical and bioinformatic methods that are being used to identify previously uncharacterized secondary metabolite gene clusters and their associated metabolites. It is important to identify as many of these compounds as possible to determine their bioactivity with respect to fungal development, survival, virulence and especially with respect to any potential synergistic toxic effects with aflatoxin.

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Kojic acid biosynthesis in Aspergillus oryzae is regulated by a Zn(II)2Cys6 transcriptional activator and induced by kojic acid at the transcriptional level

Cited by 74 publications

References 13 publications

The non-metabolizable glucose analog D-glucal inhibits aflatoxin biosynthesis and promotes kojic acid production in Aspergillus flavus

The non-metabolizable glucose analog D-glucal inhibits aflatoxin biosynthesis and promotes kojic acid production in Aspergillus flavus

Advances in Aspergillus secondary metabolite research in the post-genomic era

<i>Aspergillus flavus</i> Secondary Metabolites: More than Just Aflatoxins

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