Identification and characterization of genes responsible for biosynthesis of kojic acid, an industrially important compound from Aspergillus oryzae

Terabayashi, Yasunobu; Sano, Motoaki; Yamane, Noriko; Marui, Junichiro; Tamano, Koichi; Sagara, Jun‐ichi; Dohmoto, Mitsuko; Oda, Kiyoshi; Ohshima, Eiji; Tachibana, Kuniharu; Higa, Yoshitaka; Ohashi, Satoshi; Koike, Hideaki; Machida, Masayuki

doi:10.1016/j.fgb.2010.08.014

Cited by 151 publications

(163 citation statements)

References 45 publications

(38 reference statements)

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“…4) According to another study, KA production was lost in the laeA disruption (ÁLaeA) strain in A. flavus, 5) but it was uncertain how LaeA controlled KA production. To elucidate laeA regulation of KA production in A. oryzae, we produced a disruption mutant.…”

Section: )mentioning

confidence: 99%

“…Preliminary studies have indicated that AO090113000137 (a transcription factor) activated AO090113000136 (an enzyme) and AO090113000138 (a transporter). 4) The influence of the laeA deletion on the expression of KA biosynthesis genes was analyzed by real-time PCR. The ÁLaeA and PyrGþ strains were cultivated at 30 C for 72 h under KA-producing conditions.…”

Section: )mentioning

confidence: 99%

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Aspergillus oryzae laeARegulates Kojic Acid Synthesis Genes

Oda

Kobayashi

Ohashi

et al. 2011

Bioscience, Biotechnology, and Biochemistry

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confidence: 99%

Section: )mentioning

confidence: 99%

Aspergillus oryzae laeARegulates Kojic Acid Synthesis Genes

Oda

Kobayashi

Ohashi

et al. 2011

Bioscience, Biotechnology, and Biochemistry

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“…Specifically, 55 different clusters were predicted based on the presence of genes encoding polyketide synthases (PKSs), nonribosomal peptide synthetases (NRPSs), hybrid PKS-NRPSs, and prenyltransferases (PTRs) within the clusters (13,14). An additional gene cluster, responsible for the synthesis of kojic acid, has also been recently identified (15). In spite of these new findings, only a few metabolites have been associated with these clusters (16), among them the clusters associated with the synthesis of kojic acid, as well as the synthesis of AFs, CPA, aflatrem, and asparasone.…”

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Transcriptome Analysis of Aspergillus flavus Reveals veA -Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

et al. 2015

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eThe global regulatory veA gene governs development and secondary metabolism in numerous fungal species, including Aspergillus flavus. This is especially relevant since A. flavus infects crops of agricultural importance worldwide, contaminating them with potent mycotoxins. The most well-known are aflatoxins, which are cytotoxic and carcinogenic polyketide compounds. The production of aflatoxins and the expression of genes implicated in the production of these mycotoxins are veA dependent. The genes responsible for the synthesis of aflatoxins are clustered, a signature common for genes involved in fungal secondary metabolism. Studies of the A. flavus genome revealed many gene clusters possibly connected to the synthesis of secondary metabolites. Many of these metabolites are still unknown, or the association between a known metabolite and a particular gene cluster has not yet been established. In the present transcriptome study, we show that veA is necessary for the expression of a large number of genes. Twenty-eight out of the predicted 56 secondary metabolite gene clusters include at least one gene that is differentially expressed depending on presence or absence of veA. One of the clusters under the influence of veA is cluster 39. The absence of veA results in a downregulation of the five genes found within this cluster. Interestingly, our results indicate that the cluster is expressed mainly in sclerotia. Chemical analysis of sclerotial extracts revealed that cluster 39 is responsible for the production of aflavarin.A spergillus flavus is a saprophytic filamentous fungus that is also able to colonize economically important crops such as peanuts, cotton, maize, and other oil seed crops during preharvest or storage. Its most efficient mode of dissemination is the production of airborne conidia. In addition, A. flavus produces resistant structures called sclerotia, which allow this fungus to survive adverse environmental conditions for long periods of time (1-3). This opportunistic pathogen produces a wide range of secondary metabolites, including aflatoxins (AFs). Among them, AFB1 is the most mutagenic and carcinogenic natural compound known (4-8). Ingestion of food products contaminated with AFs has been associated with hepatotoxicity, teratogenicity, immunosuppression, and liver cancer (6, 9). AF contamination also results in a negative impact on the economy in developed countries. In the United States alone A. flavus causes more than a billion dollar in losses per year due to contaminated crops (10). In addition to AFs, A. flavus is known to produce other mycotoxins, including cyclopiazonic acid (CPA), a suppressor of the calcium-dependent ATPase in the sarcoplasmic reticulum, and aflatrem, a tremogenic mycotoxin causative of neurological disorders (11,12).Studies of the A. flavus genome have revealed many gene clusters possibly connected to the synthesis of other secondary metabolites. Specifically, 55 different clusters were predicted based on the presence of genes encoding polyketide synthases (PKSs), non...

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“…Latterly, the whitening agent in this acid benefits as an essential ingredient in cosmetic cream to block the formation of pigments by the deep cells on the skin [2]. It was studied intensively by several researches due to its potential as a tyrosinase inhibitor to prevent browning in food production as well as a skin lightening agent for cosmetic preparations [3][4][5]. In Asia, hyroquinone, a well-known whitening agent, was banned for cosmetic usage for its toxicity.…”

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confidence: 99%

Evaluation of Direct Esterification of Fatty Acid Derivative of Kojic Acid in Co-solvent System: A Statistical Approach

Norddin¹,

Azhar²,

Ashari³

2017

J Chem Eng Process Technol

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The present work deals with direct esterification method to synthesize Kojic acid using immobilized lipase as a biocatalyst in acetonitrile with the addition of dimethylsulfoxide (DMSO) as a solubilizing agent Co-solvent respectively. To increase the esterification yield of KMO, modifications of the process were evaluated, including the use of a cosolvent and the use of Novozyme 435 (Candida antarctica) as a catalyst. The KMO synthesis has been developed and optimized by using Response Surface Methodology (RSM) with Central Composite Rotatable Design (CCRD). The optimized condition of enzyme was 3.35 wt% and 1:3.64 molar ratio of kojic acid and oleic acid at 82.39°C for 255.24 min of reaction. With these condition, the maximum percentage yield was 42.73% with R2 value of 0.866914 and indicated that 86.69% of the variability in the response could be explained by the model. The model was significant and fitted well with the experimental data and the lack of fit was not significant. The efficacy for cosmetic application was successfully tested and showed as non-irritating with a Human Irritancy Equivalent score between 0.55-0.83 which safe to be applied in cosmetic ingredient.

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Identification and characterization of genes responsible for biosynthesis of kojic acid, an industrially important compound from Aspergillus oryzae

Cited by 151 publications

References 45 publications

Aspergillus oryzae laeARegulates Kojic Acid Synthesis Genes

Aspergillus oryzae laeARegulates Kojic Acid Synthesis Genes

Transcriptome Analysis of Aspergillus flavus Reveals veA -Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

Evaluation of Direct Esterification of Fatty Acid Derivative of Kojic Acid in Co-solvent System: A Statistical Approach

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