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Shimalactone Biosynthesis Involves Spontaneous Double Bicyclo‐Ring Formation with 8π‐6π Electrocyclization
Author(s) -
Fujii Isao,
Hashimoto Makoto,
Konishi Kaori,
Unezawa Akiko,
Sakuraba Haruka,
Suzuki Kenta,
Tsushima Harue,
Iwasaki Miho,
Yoshida Satsuki,
Kudo Akane,
Fujita Rina,
Hichiwa Aika,
Saito Koharu,
Asano Takashi,
Ishikawa Jun,
Wakana Daigo,
Goda Yukihiro,
Watanabe Ayumi,
Watanabe Mamoru,
Masumoto Yui,
Kanazawa Junichiro,
Sato Hajime,
Uchiyama Masanobu
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202001024
Subject(s) - bicyclic molecule , aspergillus oryzae , chemistry , stereochemistry , ring (chemistry) , epoxide , polyketide synthase , polyketide , protonation , heterologous expression , biosynthesis , gene cluster , aspergillus nidulans , enzyme , biochemistry , gene , organic chemistry , mutant , recombinant dna , catalysis , ion
Shimalactones A and B are neuritogenic polyketides possessing characteristic oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene ring systems that are produced by the marine fungus Emericella variecolor GF10. We identified a candidate biosynthetic gene cluster and conducted heterologous expression analysis. Expression of ShmA polyketide synthase in Aspergillus oryzae resulted in the production of preshimalactone. Aspergillus oryzae and Saccharomyces cerevisiae transformants expressing ShmA and ShmB produced shimalactones A and B, thus suggesting that the double bicyclo‐ring formation reactions proceed non‐enzymatically from preshimalactone epoxide. DFT calculations strongly support the idea that oxabicyclo‐ring formation and 8π‐6π electrocyclization proceed spontaneously after opening of the preshimalactone epoxide ring through protonation. We confirmed the formation of preshimalactone epoxide in vitro, followed by its non‐enzymatic conversion to shimalactones in the dark.