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Biosynthesis of triacsin featuring an N-hydroxytriazene pharmacophore.
Del Rio Flores, Antonio; Twigg, Frederick F; Du, Yongle; Cai, Wenlong; Aguirre, Daniel Q; Sato, Michio; Dror, Moriel J; Narayanamoorthy, Maanasa; Geng, Jiaxin; Zill, Nicholas A; Zhai, Rui; Zhang, Wenjun.
Afiliação
  • Del Rio Flores A; Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, United States.
  • Twigg FF; Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, United States.
  • Du Y; Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, United States.
  • Cai W; Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, United States.
  • Aguirre DQ; Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, United States.
  • Sato M; Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
  • Dror MJ; Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, United States.
  • Narayanamoorthy M; Department of Chemistry, University of California Berkeley, Berkeley, CA, United States.
  • Geng J; Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, CA, United States.
  • Zill NA; Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, United States.
  • Zhai R; Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, United States.
  • Zhang W; Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, United States. wjzhang@berkeley.edu.
Nat Chem Biol ; 17(12): 1305-1313, 2021 12.
Article em En | MEDLINE | ID: mdl-34725510
Triacsins are an intriguing class of specialized metabolites possessing a conserved N-hydroxytriazene moiety not found in any other known natural products. Triacsins are notable as potent acyl-CoA synthetase inhibitors in lipid metabolism, yet their biosynthesis has remained elusive. Through extensive mutagenesis and biochemical studies, we here report all enzymes required to construct and install the N-hydroxytriazene pharmacophore of triacsins. Two distinct ATP-dependent enzymes were revealed to catalyze the two consecutive N-N bond formation reactions, including a glycine-utilizing, hydrazine-forming enzyme (Tri28) and a nitrite-utilizing, N-nitrosating enzyme (Tri17). This study paves the way for future mechanistic interrogation and biocatalytic application of enzymes for N-N bond formation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Streptomyces aureofaciens / Triazenos / Coenzima A Ligases Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Streptomyces aureofaciens / Triazenos / Coenzima A Ligases Idioma: En Ano de publicação: 2021 Tipo de documento: Article