Total Biosynthesis of Diterpene Aphidicolin, a Specific Inhibitor of DNA Polymerase α: Heterologous Expression of Four Biosynthetic Genes in Aspergillus oryzae

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概要

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• Clustering of biosynthetic genes for producing fungal secondary metabolites, which frequently consist of less than ten genes, has been recognized with numerous genomes. The heterologous expression of whole genes in the clusters will therefore produce various types of natural products when using a suitable fungal host. We introduced the whole gene cluster for the biosynthesis of diterpene aphidicolin into the fungal quadruple auxotrophic host, Aspergillus oryzae, by using four different vectors (pTAex3, pPTRI, pUSA and pAdeA) which harbor a starch-inducible promoter/terminator to examine the expression conditions. The resulting quadruple transformant carrying the genes of geranylgeranyl diphosphate synthase PbGGS, terpene synthase PbACS, and two monooxygenases (PbP450-1 and PbP450-2) produced aphidicolin. The double and triple transformants also respectively produced aphidicolan-16β-ol and 3-deoxyaphidicolin. Alternative host Saccharomyces cerevisiae carrying the genes, PbGGS and PbACS, produced key intermediate aphidicolan-16β-ol. This is the first example of a total biosynthesis of terpenoids using fungal hosts.

• 社団法人 日本農芸化学会の論文

著者

• Oikawa Hideaki

  Division Of Applied Bioscience Graduate School Of Agriculture Hokkaido University

• Gomi Katsuya

  Graduate School Of Agricultural Science Tohoku University

• FUJII Ryuya

  Division of Chemistry, Graduate School of Science, Hokkaido University

• MINAMI Atsushi

  Division of Chemistry, Graduate School of Science, Hokkaido University

• TSUKAGOSHI Tae

  Division of Chemistry, Graduate School of Science, Hokkaido University

• SATO Natsuko

  Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (

• SAHARA Takehiko

  Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (

• OHGIYA Satoru

  Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (

• Tsukagoshi Tae

  Division Of Chemistry Graduate School Of Science Hokkaido University

関連論文

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