2012
DOI: 10.1002/anie.201108214
|View full text |Cite
|
Sign up to set email alerts
|

Antiterminator‐Mediated Unveiling of Cryptic Polythioamides in an Anaerobic Bacterium

Abstract: Anti‐Terminator: Rise of the Molecules: Overexpression of an antiterminator gene (nusG) in Clostridium cellulolyticum induced the biosynthesis of the novel antibiotic closthioamide and related thioamides. This is the first successful genetic engineering of an anaerobe to trigger a cryptic pathway. Furthermore, synthetic probes provide valuable insights into the biogenetic relationship of the rare thioamide metabolites.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

0
20
0

Year Published

2012
2012
2018
2018

Publication Types

Select...
7

Relationship

5
2

Authors

Journals

citations
Cited by 48 publications
(21 citation statements)
references
References 22 publications
0
20
0
Order By: Relevance
“…For example, many non-pathogenic Clostridia encode an abundance of cryptic PKS gene clusters that exhibit evidence of horizontal gene transfer 36 , a subset of which are associated with a loaP homologue. In an earlier study, a novel C. cellulolyticum poly-thioamide (closthioamide) was produced upon overexpression of a NusG homologue 28 , which our phylogenetic analysis revealed to be within the LoaP subclass, providing further evidence for a regulatory relationship between loaP and PKS genes.…”
Section: Discussionmentioning
confidence: 52%
See 1 more Smart Citation
“…For example, many non-pathogenic Clostridia encode an abundance of cryptic PKS gene clusters that exhibit evidence of horizontal gene transfer 36 , a subset of which are associated with a loaP homologue. In an earlier study, a novel C. cellulolyticum poly-thioamide (closthioamide) was produced upon overexpression of a NusG homologue 28 , which our phylogenetic analysis revealed to be within the LoaP subclass, providing further evidence for a regulatory relationship between loaP and PKS genes.…”
Section: Discussionmentioning
confidence: 52%
“…Although antitermination activity has yet to be observed for TaA, this discovery suggested proof in principle that transcription elongation factors may affect specialized metabolite pathways. In a separate study, general overexpression of a NusG homologue led to discovery of a new Clostridium cellulolyticum natural product 28 . Inspired by these findings, we hypothesized that more antitermination systems await discovery and that they will prove to be essential for the transcription of important pathways, including those encoding specialized metabolites.…”
Section: Discussionmentioning
confidence: 99%
“…From a conformational perspective, more interesting are the two endothioxopeptides thioviridamide, from the actinomycete Streptomyces olivoviridis , and closthioamide, an antibiotic from Clostridium cellulolyticum . Thioviridamide is partly similar to methanobactin, but only because it is formed by a cyclic moiety and a pendant linear chain.…”
Section: Resultsmentioning
confidence: 99%
“…The thionamide bonds are among the factors responsible for the antibacterial property of this endothioxopeptide since the all-amide synthetic analog is inactive. Seven closthioamide congeners (2)(3)(4)(5)(6)(7)(8) with varying numbers of thionamide linkages also occur in Nature [29] (Figure 2). A large set of closthioamide analogs were synthesized to reveal in detail the crucial motifs for its antibiotic activity.…”
Section: Naturally Occurring Endothioxopeptidesmentioning
confidence: 99%
“…In recent years,ag rowing number of thioamide-bearing natural products have been discovered. [11] In cases where it has been investigated, the thioamide functionality in these compounds has been shown to be an essential pharmacophore or chelating residue. [11d, 12] Whereas the chemical synthesis of thioamides with phosphorus sulfides (Lawessonsr eagent) and other reagents is already well established, [13] the biochemical basis of enzymatic amide thionation has remained obscure.O nly recently,p osttranslational thioamidations of the protein methyl-coenzyme Mr eductase [14] and the ribosomal peptide methanobactin [15] have been uncovered.…”
mentioning
confidence: 99%