<i>Aspergillus oryzae laeA</i>Regulates Kojic Acid Synthesis Genes

Oda, Kiyoshi; Kobayashi, Akito; Ohashi, Satoshi; Sano, Motoaki

doi:10.1271/bbb.110235

Cited by 59 publications

(43 citation statements)

References 10 publications

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“…It was previously reported that kojic acid production is regulated by LaeA, but we found that laeA coordinates both SM production and conidial development (39). In general, the production of fungal SMs is coordinated with fungal development, and the LaeA complex coordinates these (17).…”

Section: Discussionmentioning

confidence: 52%

Fungus-Specific Sirtuin HstD Coordinates Secondary Metabolism and Development through Control of LaeA

2013

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bThe sirtuins are members of the NAD ؉ -dependent histone deacetylase family that contribute to various cellular functions that affect aging, disease, and cancer development in metazoans. However, the physiological roles of the fungus-specific sirtuin family are still poorly understood. Here, we determined a novel function of the fungus-specific sirtuin HstD/Aspergillus oryzae Hst4 (AoHst4), which is a homolog of Hst4 in A. oryzae yeast. The deletion of all histone deacetylases in A. oryzae demonstrated that the fungus-specific sirtuin HstD/AoHst4 is required for the coordination of fungal development and secondary metabolite production. We also show that the expression of the laeA gene, which is the most studied fungus-specific coordinator for the regulation of secondary metabolism and fungal development, was induced in a ⌬hstD strain. Genetic interaction analysis of hstD/ Aohst4 and laeA clearly indicated that HstD/AoHst4 works upstream of LaeA to coordinate secondary metabolism and fungal development. The hstD/Aohst4 and laeA genes are fungus specific but conserved in the vast family of filamentous fungi. Thus, we conclude that the fungus-specific sirtuin HstD/AoHst4 coordinates fungal development and secondary metabolism via the regulation of LaeA in filamentous fungi.

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Section: Discussionmentioning

confidence: 52%

Fungus-Specific Sirtuin HstD Coordinates Secondary Metabolism and Development through Control of LaeA

2013

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“…It should be noted here that heterochromatin formation in filamentous fungi is without doubt best understood in N. crassa (Rountree and Selker 2010), but this organism is not a suitable model for secondary metabolism. In contrast to LaeA, which is well studied at the genetic, genomic, and physiological level and known to regulate chemical diversity in a large range of fungi (Bok and Keller 2004; Kale et al 2007; Kale et al 2008; Kosalkova et al 2009; Oda et al 2011; Perrin et al 2007; Wiemann et al 2010; Xing et al 2010), factors regulating heterochromatin formation in SM gene clusters have only been studied in the human opportunistic pathogen Aspergillus fumigatus and the plant pathogen Fusarium graminearum . Deletion of the A. fumigatus H3K9 methyltransferase ClrD reduced viability and conidia production but did not change host interactions in a macrophage assay (Palmer et al 2008).…”

Section: Does Heterochromatin Also Regulate Sm In Other Fungi?mentioning

confidence: 99%

The chromatin code of fungal secondary metabolite gene clusters

Gacek

Strauss

2012

Appl Microbiol Biotechnol

167

125

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Secondary metabolite biosynthesis genes in fungi are usually physically linked and organized in large gene clusters. The physical linkage of genes involved in the same biosynthetic pathway minimizes the amount of regulatory steps necessary to regulate the biosynthetic machinery and thereby contributes to physiological economization. Regulation by chromatin accessibility is a proficient molecular mechanism to synchronize transcriptional activity of large genomic regions. Chromatin regulation largely depends on DNA and histone modifications and the histone code hypothesis proposes that a certain combination of modifications, such as acetylation, methylation or phosphorylation, is needed to perform a specific task. A number of reports from several laboratories recently demonstrated that fungal secondary metabolite (SM) biosynthesis clusters are controlled by chromatin-based mechanisms and histone acetyltransferases, deacetylases, methyltransferases, and proteins involved in heterochromatin formation were found to be involved. This led to the proposal that establishment of repressive chromatin domains over fungal SM clusters under primary metabolic conditions is a conserved mechanism that prevents SM production during the active growth phase. Consequently, transcriptional activation of SM clusters requires reprogramming of the chromatin landscape and replacement of repressive histone marks by activating marks. This review summarizes recent advances in our understanding of chromatin-based SM cluster regulation and highlights some of the open questions that remain to be answered before we can draw a more comprehensive picture.

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“…The lae1 / laeA ( l oss of a flR e xpression) gene was originally identified in A. nidulans (Bok et al, 2005). This gene was later proven to affect morphological development and the biosynthesis of a large number of secondary metabolites in many filamentous fungi, such as Aspergilli (Kale et al, 2008; Oda et al, 2011; Chang et al, 2012), Penicillium chrysogenum (Kosalková et al, 2009), and Fusarium verticillioides (Butchko et al, 2012). LaeA's function is always associated to the epigenetic control by its putative protein methyltransferase function (specifically for histone tails), as LaeA possesses S-adenosyl-methionine-binding (SAM) motifs.…”

Section: Introductionmentioning

confidence: 99%

The Different Roles of Penicillium oxalicum LaeA in the Production of Extracellular Cellulase and β-xylosidase

Zheng

Zhang

et al. 2016

Front. Microbiol.

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Cellulolytic enzyme hydrolysis of lignocellulose biomass to release fermentable sugars is one of the key steps in biofuel refining. Gene expression of fungal cellulolytic enzymes is tightly controlled at the transcriptional level. Key transcription factors such as activator ClrB/CLR2 and XlnR/XYR1, as well as repressor CreA/CRE1 play crucial roles in this process. The putative protein methyltransferase LaeA/LAE1 has also been reported to regulate the gene expression of the cellulolytic enzyme. The formation and gene expression of the cellulolytic enzyme was compared among Penicillium oxalicum wild type (WT) and seven mutants, including ΔlaeA (deletion of laeA), OEclrB (clrB overexpression), OEclrBΔlaeA (clrB overexpression with deletion of laeA), OExlnR (xlnR overexpression), OExlnRΔlaeA (xlnR overexpression with deletion of laeA), ΔcreA (deletion of creA), and ΔcreAΔlaeA (double deletion of creA and laeA). Results revealed that LaeA extensively affected the expression of glycoside hydrolase genes. The expression of genes that encoded the top 10 glycoside hydrolases assayed in secretome was remarkably downregulated especially in later phases of prolonged batch cultures by the deletion of laeA. Cellulase synthesis of four mutants ΔlaeA, OEclrBΔlaeA, OExlnRΔlaeA, and ΔcreAΔlaeA was repressed remarkably compared with their parent strains WT, OEclrB, OExlnR, and ΔcreA, respectively. The overexpression of clrB or xlnR could not rescue the impairment of cellulolytic enzyme gene expression and cellulase synthesis when LaeA was absent, suggesting that LaeA was necessary for the expression of cellulolytic enzyme gene activated by ClrB or XlnR. In contrast to LaeA positive roles in regulating prominent cellulase and hemicellulase, the extracellular β-xylosidase formation was negatively regulated by LaeA. The extracellular β-xylosidase activities improved over 5-fold in the OExlnRΔlaeA mutant compared with that of WT, and the expression of prominent β-xylosidase gene xyl3A was activated remarkably. The cumulative effect of LaeA and transcription factor XlnR has potential applications in the production of more β-xylosidase.

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Aspergillus oryzae laeARegulates Kojic Acid Synthesis Genes

Cited by 59 publications

References 10 publications

Fungus-Specific Sirtuin HstD Coordinates Secondary Metabolism and Development through Control of LaeA

Fungus-Specific Sirtuin HstD Coordinates Secondary Metabolism and Development through Control of LaeA

The chromatin code of fungal secondary metabolite gene clusters

The Different Roles of Penicillium oxalicum LaeA in the Production of Extracellular Cellulase and β-xylosidase

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