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A radical S-adenosyl-L-methionine enzyme and a methyltransferase catalyze cyclopropane formation in natural product biosynthesis

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  • Wen-Bing Jin

    (Chinese Academy of Sciences)

  • Sheng Wu

    (Chinese Academy of Sciences)

  • Xiao-Hong Jian

    (Chinese Academy of Sciences)

  • Hua Yuan

    (Chinese Academy of Sciences)

  • Gong-Li Tang

    (Chinese Academy of Sciences)

Abstract

Cyclopropanation of unactivated olefinic bonds via addition of a reactive one-carbon species is well developed in synthetic chemistry, whereas natural cyclopropane biosynthesis employing this strategy is very limited. Here, we identify a two-component cyclopropanase system, composed of a HemN-like radical S-adenosyl-l-methionine (SAM) enzyme C10P and a methyltransferase C10Q, catalyzes chemically challenging cyclopropanation in the antitumor antibiotic CC-1065 biosynthesis. C10P uses its [4Fe-4S] cluster for reductive cleavage of the first SAM to yield a highly reactive 5′-deoxyadenosyl radical, which abstracts a hydrogen from the second SAM to produce a SAM methylene radical that adds to an sp2-hybridized carbon of substrate to form a SAM-substrate adduct. C10Q converts this adduct to CC-1065 via an intramolecular SN2 cyclization mechanism with elimination of S-adenosylhomocysteine. This cyclopropanation strategy not only expands the enzymatic reactions catalyzed by the radical SAM enzymes and methyltransferases, but also sheds light on previously unnoticed aspects of the versatile SAM-based biochemistry.

Suggested Citation

  • Wen-Bing Jin & Sheng Wu & Xiao-Hong Jian & Hua Yuan & Gong-Li Tang, 2018. "A radical S-adenosyl-L-methionine enzyme and a methyltransferase catalyze cyclopropane formation in natural product biosynthesis," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05217-1
    DOI: 10.1038/s41467-018-05217-1
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    Cited by:

    1. Fang Guo & Jun Fan & Jin-Ming Liu & Peng-Li Kong & Jing Ren & Jia-Wen Mo & Cheng-Lin Lu & Qiu-Ling Zhong & Liang-Yu Chen & Hao-Tian Jiang & Canyuan Zhang & You-Lu Wen & Ting-Ting Gu & Shu-Ji Li & Ying, 2024. "Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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