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

Wen-Bing Jin, Sheng Wu, Xiao-Hong Jian, Hua Yuan () and Gong-Li Tang ()
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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

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05217-1

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