PhD Defense Xuan Loc Nguyen (S. Lautru/Dpt Microbio)

Insights into the Biosynthesis of the Pyrrolamide Antibiotics Congocidine and Kikumycin.

Membres du jury:
- Pr Bertrand Aigle
- Dr Yanyan Li
- Pr Stéphanie Bury-Moné
- Dr Evi Stegmann

Abstract:
Congocidine and kikumycin, are pyrrolamide antibiotics characterized by the presence of pyrrole moieties linked by amide bonds. Congocidine, a minor groove DNA binder, is assembled from three precursors: 3-aminopropionamidine, 4-acetamidopyrrole-2-carboxylate, and guanidinoacetate. While the biosynthetic pathways for 3-aminopropionamidine and 4-acetamidopyrrole-2-carboxylate have been elucidated, the pathway leading to guanidinoacetate remains partially unresolved.
Our work has demonstrated that Cgc6 catalyzes the conversion of demethylcreatinine into guanidinoacetate. We now propose that Cgc7, a predicted structural analog of FemX, synthesizes demethylcreatinine using arginine and tRNA-Gly as substrates.
In parallel, the biosynthetic gene cluster for kikumycin has yet to be identified. Through genomic analysis, we discovered a candidate biosynthetic gene cluster in Streptomyces sp. TLI146, which we cloned and heterologously expressed in Streptomyces lividans and Streptomyces albus.
I will present my progress on elucidating the biosynthesis of these two pyrrolamide antibiotics, focusing on the Cgc7 enzymatic characterization and on the putative kikumycin gene cluster identification and characterization.