4.8 Article

Characterization of Enzymes Catalyzing the Initial Steps of the β-Lactam Tabtoxin Biosynthesis

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ORGANIC LETTERS
卷 24, 期 18, 页码 3337-3341

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.orglett.2c00878

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资金

  1. Ministry of Education, Culture, Sports, Science and Technology, Japan (JSPS KAKENHI) [20H00490, 20KK0173, 21K18246, 20K22700, 21K14744]
  2. New Energy and Industrial Technology Development Organization (NEDO) [JPNP20011]
  3. Japan Agency for Medical Research and Development (AMED) [JP21ak0101164]
  4. Japan Science and Technology Agency [JPMJAX2013]
  5. Kobayashi Foundation

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This study describes the early stages of Tabtoxin biosynthesis and identifies the roles of TblA and TblD in the process through gene deletion and in vitro biochemical assays, providing insights into the progression of these reactions.
Tabtoxin is a beta-lactam ring-containing phytotoxin produced by a plant pathogenic Pseudomonas species. Here, we describe the early stages of tabtoxin biosynthesis, involving a C-methylation reaction catalyzed by the S-adenosyl-L-methionine-dependent methyltransferase TblA as the initial step for the beta-lactam construction. Gene deletion and in vitro biochemical assays demonstrated that the Gcn5-related N-acetyltransferase domain of TblD catalyzes the acetylation of the alpha-amino group of 5-methyl-L-lysine. This establishment of the early reaction steps lays the foundation for characterizing unique beta-lactam biosynthesis.

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