Abstract
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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Acknowledgments
The study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology (MEXT) and by a joint program in the field of biotechnology under the Japan Society for the Promotion of Science, the National Research Council of Thailand, and the National Science and Technology Development Agency of Thailand. This paper represents a portion of KS’s Ph.D. dissertation.
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Sakai, K., Kinoshita, H. & Nihira, T. Heterologous expression system in Aspergillus oryzae for fungal biosynthetic gene clusters of secondary metabolites. Appl Microbiol Biotechnol 93, 2011–2022 (2012). https://doi.org/10.1007/s00253-011-3657-9
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DOI: https://doi.org/10.1007/s00253-011-3657-9