ライフサイエンスコーパス: colibactin

1 which belongs to the same chemical family as colibactin.

2 ogenic mutant impaired for the production of colibactin.

3 d with the isogenic mutant unable to produce colibactin.

4 for small molecules named precolibactins and colibactins.

5 hase (pks) produces the secondary metabolite colibactin, a genotoxic molecule(s) causing double-stran

6 ity island and required for the synthesis of colibactin, a polyketide-peptide genotoxin that causes g

7 ichia coli residing in the human gut produce colibactin, a small-molecule genotoxin of unknown struct

8 transporter, is a key component involved in colibactin activity and transport.

9 In vitro studies using a synthetic colibactin analog and ClbS or an active site residue mut

10 investigate a possible relationship between colibactin and lymphopenia, we examined the effects of t

11 Here, we demonstrated that production of colibactin and yersiniabactin is abolished in the absenc

12 chaperone and the ClpQ protease involved in colibactin and yersiniabactin synthesis.

13 Several studies suggest colibactins are genotoxins and support a role for clb me

14 The colibactins are hybrid polyketide-nonribosomal peptide n

15 these studies suggest the active genotoxins (colibactins) are unsaturated imines that are potent DNA

16 ia coli (ExPEC), which encodes the genotoxin colibactin, are incompletely defined.

17 accommodate the synthesis of additional (pre)colibactins as they are isolated.

18 The structure harbors a potential colibactin binding site and shares similarity to known h

19 pport for individual domain contributions to colibactin biosynthesis and delineated the assembly line

20 The data support unexpected models for both colibactin biosynthesis and its mode of action.

21 Though advances toward elucidating (pre)colibactin biosynthesis have been made, the functions an

22 Colibactin biosynthesis involves a prodrug resistance st

23 Colibactin biosynthesis is hypothesized to involve a pro

24 s, elongation, and cleavage enzymes from the colibactin biosynthetic pathway.

25 myristoyl-d-asparagine and its corresponding colibactin by colibactin peptidase ClbP.

26 onclusion, we demonstrate that production of colibactin by E. coli exacerbates lymphopenia associated

27 hydration and antibiotics, the production of colibactin by the bacteria was associated with a signifi

28 duces precolibactins, which are converted to colibactins by a dedicated peptidase, ClbP.

29 ts precolibactins are converted to genotoxic colibactins by colibactin peptidase (ClbP)-mediated clea

30 Precolibactins are converted to colibactins by N-deacylation; the latter are postulated

31 We conclude that colibactin contributes to the capacity of E. coli K1 to

32 ctal cancer patients, suggesting that mature colibactins could initiate tumorigenesis.

33 esis in the Apc(Min/+) ;Il10(-/-) model in a colibactin-dependent manner, suggesting colibactin is a

34 To resolve this, we prepared 13 synthetic colibactin derivatives and evaluated their DNA binding a

35 It was hypothesized that colibactins form unsaturated imines that alkylate DNA by

36 Restoration of colibactin gene function by complementation reestablishe

37 sible for synthesis of the unknown molecule "colibactin" has been identified in mutualistic and patho

38 However, as no colibactins have been isolated, this hypothesis has not

39 s and biosynthesis of the precolibactins and colibactins have been made using genetic approaches, but

40 elineated the assembly line timing events of colibactin heterocycle formation.

41 E. coli producing colibactin induced a more profound lymphopenia in septic

42 We observed that colibactin induced double-strand breaks in the DNA of in

43 tabolic support of our mechanistic model for colibactin-induced genotoxicity.

44 nverts the electrophilic cyclopropane of the colibactins into an innocuous hydrolysis product.

45 in a colibactin-dependent manner, suggesting colibactin is a driver of carcinogenesis.

46 ic E. coli (ExPEC) and encodes the genotoxin colibactin, is epidemiologically associated with bactere

47 catalog of small molecules dependent on the colibactin pathway from the meningitis isolate E. coli I

48 We apply the approach to the bacterial colibactin pathway, a genotoxic NRPS-PKS hybrid pathway

49 ns are converted to genotoxic colibactins by colibactin peptidase (ClbP)-mediated cleavage of an N-ac

50 These studies indicate that deletion of the colibactin peptidase ClbP, a modification introduced to

51 paragine and its corresponding colibactin by colibactin peptidase ClbP.

52 g the 14 newly sought traits, clbB and clbN (colibactin polyketide synthesis system), hra (heat-resis

53 m, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli.

54 Precolibactins and colibactins represent a family of natural products that

55 specific mechanistic role of this enzyme in colibactin resistance.

56 , providing direct experimental evidence for colibactin's DNA-damaging activity.

57 (invasion of brain endothelium), and clbB/N (colibactin synthesis), plus molecularly defined ExPEC st

58 tion of clbP, encoding an enzyme specific to colibactin synthesis.

59 The genotoxin colibactin, synthesized by Escherichia coli, is a second

60 pks island and supports investigation of the colibactin system as a potential therapeutic target.

61 ing information about structural features of colibactin, this work reveals the biosynthetic logic und

62 S, a gene product that confers resistance to colibactin toxicity in host bacteria and which has been

63 otopic labelling studies to characterize the colibactin warhead, an unprecedented substituted spirobi

64 l peptide-polyketide hybrid pathway encodes 'colibactin', which belongs to a largely uncharacterized