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Article Dans Une Revue Scientific Reports Année : 2019

Study of bicyclomycin biosynthesis in Streptomyces cinnamoneus by genetic and biochemical approaches

Antonio Ruzzini
  • Fonction : Auteur
Olivier Lequin

Résumé

The 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.
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Origine : Publication financée par une institution

Dates et versions

hal-02431235 , version 1 (18-11-2020)

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Jerzy Witwinowski, Mireille Moutiez, Matthieu Coupet, Isabelle Correia, Pascal Belin, et al.. Study of bicyclomycin biosynthesis in Streptomyces cinnamoneus by genetic and biochemical approaches. Scientific Reports, 2019, 9 (1), pp.20226. ⟨10.1038/s41598-019-56747-7⟩. ⟨hal-02431235⟩
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