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Elucidation of Biosynthetic Pathways of Natural Products
Author(s) -
Kishimoto Shinji,
Tsunematsu Yuta,
Sato Michio,
Watanabe Kenji
Publication year - 2017
Publication title -
the chemical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.61
H-Index - 78
eISSN - 1528-0691
pISSN - 1527-8999
DOI - 10.1002/tcr.201700015
Subject(s) - fumagillin , aspergillus nidulans , biosynthesis , heterologous , biochemistry , saccharomyces cerevisiae , natural product , heterologous expression , computational biology , metabolic pathway , biology , metabolic engineering , chemistry , enzyme , gene , genetics , recombinant dna , mutant , angiogenesis
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.)