Author:
Witwinowski Jerzy,Moutiez Mireille,Coupet Matthieu,Correia Isabelle,Belin Pascal,Ruzzini Antonio,Saulnier Corinne,Caraty Laëtitia,Favry Emmanuel,Seguin Jérôme,Lautru Sylvie,Lequin Olivier,Gondry Muriel,Pernodet Jean-Luc,Darbon Emmanuelle
Abstract
AbstractThe 2,5-Diketopiperazines (DKPs) constitute a large family of natural products with important biological activities. Bicyclomycin is a clinically-relevant DKP antibiotic that is the first and only member in a class known to target the bacterial transcription termination factor Rho. It derives from cyclo-(l-isoleucyl-l-leucyl) and has an unusual and highly oxidized bicyclic structure that is formed by an ether bridge between the hydroxylated terminal carbon atom of the isoleucine lateral chain and the alpha carbon of the leucine in the diketopiperazine ring. Here, we paired in vivo and in vitro studies to complete the characterization of the bicyclomycin biosynthetic gene cluster. The construction of in-frame deletion mutants in the biosynthetic gene cluster allowed for the accumulation and identification of biosynthetic intermediates. The identity of the intermediates, which were reproduced in vitro using purified enzymes, allowed us to characterize the pathway and corroborate previous reports. Finally, we show that the putative antibiotic transporter was dispensable for the producing strain.
Publisher
Springer Science and Business Media LLC
Cited by
12 articles.
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