2012
DOI: 10.1021/cb300173x
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Biosynthesis of Albomycin δ2 Provides a Template for Assembling Siderophore and Aminoacyl-tRNA Synthetase Inhibitor Conjugates

Abstract: “Trojan horse” antibiotic albomycins are peptidyl nucleosides consisting of a highly modified 4′-thiofuranosyl cytosine moiety and a ferrichrome siderophore that are linked by a peptide bond via a serine residue. While the latter component serves to sequester iron from the environment, the seryl nucleoside portion is a potent inhibitor of bacterial seryl-tRNA synthetases, resulting in broad-spectrum antimicrobial activities of albomycin δ2. The isolation of albomycins has revealed this biological activity is o… Show more

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Cited by 61 publications
(85 citation statements)
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“…1A) revealed the presence of the gene for lytic murein transglycosylase D (MltD), which is involved in bacterial cell wall degradation (21). The mltD gene is not part of the npp operon, which is expressed as a single polycistronic nppA1A2BCD-fabI transcript (8, 9, 17) from three promoters ( 32 , 38 , and 70 ) located in the intergenic region between mltD and nppA (22). The nppA1A2BCD-fabI operon is expressed at a low level in cells of P. aeruginosa PA14 during growth in LB medium, as previously shown by RNA sequencing (8).…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…1A) revealed the presence of the gene for lytic murein transglycosylase D (MltD), which is involved in bacterial cell wall degradation (21). The mltD gene is not part of the npp operon, which is expressed as a single polycistronic nppA1A2BCD-fabI transcript (8, 9, 17) from three promoters ( 32 , 38 , and 70 ) located in the intergenic region between mltD and nppA (22). The nppA1A2BCD-fabI operon is expressed at a low level in cells of P. aeruginosa PA14 during growth in LB medium, as previously shown by RNA sequencing (8).…”
Section: Resultsmentioning
confidence: 99%
“…Albomycin, a naturally occurring peptidyl nucleoside sideromycin structurally related to the hydroxamate siderophore ferrichrome, consists of an aminoacyl-nucleotide antibiotic moiety linked to a ferrichrome siderophore (37,38). The high specific activity of albomycin against E. coli comes from its ability to use the ferric hydroxamate import system for its uptake across both the outer membrane and the cytoplasmic membrane.…”
Section: Discussionmentioning
confidence: 99%
“…This concept is based on the naturally occurring sideromycin antibiotics that mimic siderophores to gain intracellular access (Braun et al, 2009). Over the past three decades, numerous conjugates linking a siderophore or a siderophore mimic to different antibiotics via a linker molecule have been synthesized with varying degrees of antimicrobial efficacy (Möllmann et al, 2009;Wencewicz et al, 2009;Zeng et al, 2012;Fardeau et al, 2014). This approach, known as the 'Trojan horse' strategy, has been the subject of several reviews (including those by de Carvalho & Fernandes, 2014;Gó rska et al, 2014;Mislin & Schalk, 2014).…”
Section: Novel Therapeutic Strategies Targeting Iron Acquisition In Cmentioning
confidence: 99%
“…In some cases, the ribosomal binding site (RBS) of a target gene was included within the 3= end of a fragment following the restriction site. Control plasmid pA10 is the pSE34-oriT vector containing abmK (19). The direct sulfhydrylation genes metYXSO were amplified as a single 4-kb DNA fragment and cloned into pSE34-oriT to obtain pCK1.…”
Section: Methodsmentioning
confidence: 99%
“…We initiated research on ABM biosynthesis with one aim: to improve ABM production in a native producer, S. griseus ATCC 700974 (19)(20)(21). A draft genome sequence of S. griseus was obtained, and the ABM biosynthetic gene cluster (abm) was identified.…”
mentioning
confidence: 99%