(250f) Biosynthesis of Triacsin Featuring an N-Hydroxytriazene Pharmacophore
AIChE Annual Meeting
2022
2022 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Advances in Biocatalysts and Biocatalytic Processes
Tuesday, November 15, 2022 - 9:30am to 9:48am
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.
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.