Journal
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
Volume 93, Issue 5, Pages 2011-2022Publisher
SPRINGER
DOI: 10.1007/s00253-011-3657-9
Keywords
Aspergillus oryzae; Secondary metabolite; Heterologous expression; laeA
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Funding
- Ministry of Education, Sports, Culture, Science and Technology (MEXT)
- Japan Society for the Promotion of Science
- National Research Council of Thailand
- National Science and Technology Development Agency of Thailand
- Grants-in-Aid for Scientific Research [21360404] Funding Source: KAKEN
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Fungal secondary metabolites have been considered promising resources in the search for novel bioactive compounds. Given the high potential of fungi as genetic resources, it is essential to find an efficient way to link biosynthetic genes to the product in a heterologous system, because many genes for the secondary metabolite in the original strain are silent under standard laboratory conditions. In a previous study, we constructed a heterologous expression system for a biosynthetic gene cluster using Aspergillus oryzae as the host. To make the host more versatile for the expression of secondary metabolism genes, the expression levels of a global regulator, laeA, were increased by placing the A. oryzae laeA gene under the control of the constitutive active pgk promoter. In the A. oryzae overexpressing laeA, two clusters of heterologous biosynthetic genes [the monacolin K (MK) gene cluster from Monascus pilosus and the terrequinone A (TQ) gene cluster from Aspergillus nidulans] were successfully overexpressed, resulting in the production of the corresponding metabolite, MK or TQ. The successful production of secondary metabolites belonging to different structural groups, namely MK as a polyketide and TQ as a hybrid of amino acid and isoprenoid, indicated that the laeA-enriched A. oryzae was a versatile host for the heterologous expression of the biosynthetic gene cluster.
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