Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024312 (
lymphopenia
)
4,859
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Colibactin represents a structurally undefined class of bacterial genotoxin inducing DNA damage and genomic instability in mammalian cells, thus promoting tumour development and exacerbating
lymphopenia
in animal models. The colibactin biosynthetic gene cluster (
clb
) has been known for ten years and it encodes a hybrid nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) assembly line. Nevertheless, the final chemical product(s) remain unknown. Previously, we and others reported several colibactin pathway-related metabolites including
N
-myristoyl-d-asparagine (
1
) as part of a prodrug precursor that is cleaved from the putative precolibactin to form active colibactin by the peptidase ClbP. Herein, we report two new colibactin pathway-related metabolites (
2
and
3
) isolated from a
clbP
mutant of the probiotic
E. coli
Nissle 1917 strain. Their structures were established by HRMS and NMR. Compound
2
shows an additional 4-aminopenatanoic acid moiety with respect to
1
, while
3
is characterized by the presence of an unusual 7-methyl-4-azaspiro[2.4]hept-6-en-5-one residue. Moreover, we propose the biosynthetic pathway towards both intermediates on the basis of extensive gene inactivation and feeding experiments. The identification of
2
and
3
provides further insight into colibactin biosynthesis including the involvement and formation of a rare
1-aminocyclopropanecarboxylic acid
unit. Thus, our work establishes additional steps of the pathway forming the bacterial genotoxin colibactin.
...
PMID:Two more pieces of the colibactin genotoxin puzzle from
Escherichia coli
show incorporation of an unusual 1-aminocyclopropanecarboxylic acid moiety. 2870 87
