title: Elucidation of Biosynthetic Pathways of Natural Products.
abstract: During the last decade, we have revealed biosynthetic pathways responsible for the formation of important and chemically complex natural products isolated from various organisms through genetic manipulation. Detailed in vivo and in vitro characterizations enabled elucidation of unexpected mechanisms of secondary metabolite biosynthesis. This personal account focuses on our recent efforts in identifying the genes responsible for the biosynthesis of spirotryprostatin, aspoquinolone, Sch 210972, pyranonigrin, fumagillin and pseurotin. We exploit heterologous reconstitution of biosynthetic pathways of interest in our study. In particular, extensive involvement of oxidation reactions is discussed. Heterologous hosts employed here are Saccharomyces cerevisiae, Aspergillus nidulans and A. niger that can also be used to prepare biosynthetic intermediates and product analogs by engineering the biosynthetic pathways using the knowledge obtained by detailed characterizations of the enzymes. (998 char.).
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, City of Shizuoka, 422-8526, JAPAN.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kishimoto
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, City of Shizuoka, 422-8526, JAPAN.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tsunematsu
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, City of Shizuoka, 422-8526, JAPAN.
authors.forename: Michio
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, City of Shizuoka, 422-8526, JAPAN.
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D001688:Biological Products / Q000032:analysis / Q000378:metabolism*; D053898:Biosynthetic Pathways; D003510:Cyclohexanes / Q000032:analysis / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000378:metabolism; D005658:Fungi / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D006576:Heterocyclic Compounds, 4 or More Rings / Q000032:analysis / Q000378:metabolism; D006912:Hydroxyquinolines / Q000032:analysis / Q000378:metabolism; D008958:Models, Molecular; D010879:Piperazines / Q000378:metabolism; D011753:Pyrones / Q000032:analysis / Q000378:metabolism; D011758:Pyrroles / Q000032:analysis / Q000378:metabolism; D064210:Secondary Metabolism; D012717:Sesquiterpenes / Q000032:analysis / Q000378:metabolism; D013141:Spiro Compounds / Q000378:metabolism
chemical_list: D001688:Biological Products; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D006576:Heterocyclic Compounds, 4 or More Rings; D006912:Hydroxyquinolines; D010879:Piperazines; D011753:Pyrones; D011758:Pyrroles; C513452:Sch 210972; D012717:Sesquiterpenes; D013141:Spiro Compounds; C522144:pyranonigrin A; C478300:spirotryprostatin A; C101781:spirotryprostatin B; C009673:viridicatin; C026211:fumagillin
keywords: biosynthesis; engineered biosynthesis; enzymatic reaction; natural product; target-guided genome mining