.png){kind=icon}
.png){kind=icon}
Return
Cpumycins A–C; Aminated Benzoic Dimers from Streptomyces sp. CPU-W6; and Their Potential Cardioprotective Activities
.png){kind=icon}
PRE
AI
Z
Y
D
Y
C
Y
J
X
DOI：10.1021/acs.jnatprod.6c00572.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Chemical investigation of the soil-derived actinomycete Streptomyces sp. CPU-W6 led to the discovery of three novel aminated benzoic dimers, cpumycins A–C (1–3). Their structures, featuring a distinctive C–N–C-linked heterodimeric skeleton, were determined through extensive spectroscopic techniques and X-ray diffraction. Bioinformatic analysis and targeted gene deletions identified a shikimate-derived biosynthetic gene cluster (CPU BGC) responsible for the assembly of these metabolites. Further investigations revealed that the formation of cpumycins 1 and 2 follows a hybrid “enzymatic-plus-spontaneous” biosynthetic paradigm, in which the enzymatic production of shikimate-derived aromatic precursors is coupled with a pH-dependent, spontaneous dimerization. In biological assays, cpumycins B (2) and C (3) exhibited cytoprotective effects against CoCl2-induced injury in undifferentiated H9c2 cells at nanomolar concentrations, while exhibiting negligible cytotoxicity (IC50 > 620 μM). These findings significantly expand the chemical diversity of shikimate-derived microbial metabolites and provide promising lead scaffolds for the development of therapeutics with potential cardioprotective benefits.
Keywords:
Aromatic compounds
Bacteria
Biosynthesis
Cluster chemistry
Peptides and proteins
Journal
IF:
3.6
Papers:
1.2W
Citations:
2.9W
Organization
Cited Papers