A ThDP-dependent enzymatic carboligation reaction involved in Neocarazostatin A tricyclic carbazole formation

Abstract

Although the biosynthetic pathway of Neocarazostatin A (1) has been identified, the detailed enzymatic reactions underlying the assembly of the carbazole ring still remain largely unknown. We demonstrate here that NzsH, a putative thiamine diphosphate dependent enzyme, can catalyze an acyloin coupling reaction between indole-3-pyruvate and pyruvate to generate a β-ketoacid intermediate. Our findings thus shed light on further characterization of the unusual biosynthetic pathway of the bacterial tricyclic carbazole alkaloids. © The Royal Society of Chemistry 2016.Although the biosynthetic pathway of Neocarazostatin A (1) has been identified, the detailed enzymatic reactions underlying the assembly of the carbazole ring still remain largely unknown. We demonstrate here that NzsH, a putative thiamine diphosphate dependent enzyme, can catalyze an acyloin coupling reaction between indole-3-pyruvate and pyruvate to generate a β-ketoacid intermediate. Our findings thus shed light on further characterization of the unusual biosynthetic pathway of the bacterial tricyclic carbazole alkaloids. © The Royal Society of Chemistry 2016.