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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Abstract

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, <I>Aspergillus oryzae</I>, 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 <I>Saccharomyces cerevisiae</I> carrying the genes, <I>PbGGS</I> and <I>PbACS</I>, produced key intermediate aphidicolan-16β-ol. This is the first example of a total biosynthesis of terpenoids using fungal hosts.

Journal

  • Bioscience, Biotechnology, and Biochemistry

    Bioscience, Biotechnology, and Biochemistry 75(9), 1813-1817, 2011-09-23

    Japan Society for Bioscience, Biotechnology, and Agrochemistry

References:  41

Cited by:  1

Codes

  • NII Article ID (NAID)
    10029757547
  • NII NACSIS-CAT ID (NCID)
    AA10824164
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09168451
  • NDL Article ID
    11252869
  • NDL Source Classification
    ZR7(科学技術--農林水産--農産) // ZR2(科学技術--生物学--生化学) // ZP1(科学技術--化学・化学工業)
  • NDL Call No.
    Z53-G223
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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