Functional Analysis of a Biosynthetic Gene Cluster Demonstrates Role of Spontaneous Double Bicyclo-ring Formation Including 8π-6π Electrocyclization in Shimalactone Biosynthesis.

Functional Analysis of a Biosynthetic Gene Cluster Demonstrates Role of Spontaneous Double Bicyclo-ring Formation Including 8π-6π Electrocyclization in Shimalactone Biosynthesis.

Angew Chem Int Ed Engl. 2020 Mar 04;:

Authors: Fujii I, Hashimoto M, Konishi K, Unezawa A, Sakuraba H, Suzuki K, Tsushima H, Iwasaki M, Yoshida S, Kudo A, Fujita R, Hichiwa A, Saito K, Asano T, Ishikawa J, Wakana D, Goda Y, Watanabe A, Watanabe M, Masumoto Y, Kanazawa J, Sato H, Uchiyama M

Abstract
Shimalactones A and B are neuritogenic polyketides possessing characteristic oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene ring systems, produced by the marine fungus Emericella variecolor GF10. We identified a candidate biosynthetic gene cluster from a draft genome analysis of the fungus, and conducted a heterologous expression analysis. Expression of ShmA polyketide synthase in Aspergillus oryzae resulted in production of preshimalactone. Aspergillus oryzae and Saccharomyces cerevisiae transformants expressing ShmA and ShmB produced shimalactones A and B, suggesting that the double bicyclo-ring formation reactions proceed non-enzymatically from preshimalactone epoxide. Density functional theory calculations strongly support the idea that oxabicyclo-ring formation and 8π-6π electrocyclization proceed spontaneously after opening of the preshimalactone epoxide ring via protonation. We confirmed the formation of preshimalactone epoxide in vitro, followed by its non-enzymatic conversion to shimalactones in the dark.

PMID: 32129542 [PubMed – as supplied by publisher]

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