期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 143, 期 50, 页码 21416-21424出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c11109
关键词
-
资金
- National Institutes of Health [GM135315, GM125924, GM127588]
BesC is a member of an emerging family of diiron enzymes that catalyze an unusual type of carbon-carbon cleavage reaction. It activates O-2 in a substrate-gated manner to generate a diferric-peroxo intermediate, initiating a unique reaction trajectory by cleaving the C4-H bond as the rate-limiting step in a single turnover reaction.
BesC catalyzes the iron- and O-2-dependent cleavage of 4-chloro-L-lysine to form 4-chloro-L-allylglycine, formaldehyde, and ammonia. This process is a critical step for a biosynthetic pathway that generates a terminal alkyne amino acid which can be leveraged as a useful bio-orthogonal handle for protein labeling. As a member of an emerging family of diiron enzymes that are typified by their heme oxygenase-like fold and a very similar set of coordinating ligands, recently termed HDOs, BesC performs an unusual type of carbon-carbon cleavage reaction that is a significant departure from reactions catalyzed by canonical dinuclear-iron enzymes. Here, we show that BesC activates O-2 in a substrate-gated manner to generate a diferric-peroxo intermediate. Examination of the reactivity of the peroxo intermediate with a series of lysine derivatives demonstrates that BesC initiates this unique reaction trajectory via cleavage of the C4-H bond; this process represents the rate-limiting step in a single turnover reaction. The observed reactivity of BesC represents the first example of a dinuclear-iron enzyme that utilizes a diferric-peroxo intermediate to capably cleave a C-H bond as part of its native function, thus circumventing the formation of a high-valent intermediate more commonly associated with substrate monooxygenations.
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