Abstract：
: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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Witwinowski J,Moutiez M,Coupet M,Correia I,Belin P,Ruzzini A,Saulnier C,Caraty L,Favry E,Seguin J,Lautru S,Lequin O,Gondry M,Pernodet JL,Darbon Edoi
10.1038/s41598-019-56747-7subject
Has Abstractpub_date
2019-12-27 00:00:00pages
20226issue
1issn
2045-2322pii
10.1038/s41598-019-56747-7journal_volume
9pub_type
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