Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mining the Cinnabaramide Biosynthetic Pathway to Generate Novel Proteasome Inhibitors
ChemBioChem, Volume 12, No. 6, Year 2011
Notification
URL copied to clipboard!
Description
The cinnabaramides and salinosporamides are mixed PKS/NRPS natural products isolated from a terrestrial streptomycete and a marine actinomycete, respectively. They interfere with the proteasome and thus potentially inhibit the growth of cancer cells. The compounds exhibit a γ-lactam-β-lactone bicyclic ring structure attached to a cyclohexenyl unit and a PKS side chain. As a first step towards improving anticancer activity and permitting genetic approaches to novel analogues, we have cloned and characterized the cinnabaramide biosynthetic genes from Streptomyces sp. JS360. In addition to the expected PKS and NRPS genes, the cluster encodes functionalities for the assembly of the hexyl side chain precursor. The corresponding enzymes exhibit relaxed substrate specificities towards a number of synthesized precursors, enabling production of novel chlorinated cinnabaramides. These were isolated and analyzed for activity, revealing that derivatives bearing a chlorine atom in the PKS side chain show higher inhibitory potentials towards the proteasome's proteolytic subunits (especially the trypsin and chymotrypsin units) and higher cytotoxicities towards human tumor cell lines than the parent cinnabaramide A. Although their activities towards the proteasome were weaker than that of salinosporamide A, the cinnabaramides were found to inhibit the growth of various fungi with greater potency. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Authors & Co-Authors
Rachid, Shwan Kamal
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Germany, Saarbrucken
Universität Des Saarlandes
Iraq, Sulaymaniyah
University of Sulaimani
Huo, Liujie
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Germany, Saarbrucken
Universität Des Saarlandes
Herrmann, Jennifer E.
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Germany, Saarbrucken
Universität Des Saarlandes
Stadler, Marc
Germany, Dortmund
Technische Universität Dortmund
Köpcke, Bärbel
Germany, Dortmund
Technische Universität Dortmund
Bitzer, Jens
Germany, Dortmund
Technische Universität Dortmund
Müller, Rolf
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Germany, Saarbrucken
Universität Des Saarlandes
Statistics
Citations: 51
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1002/cbic.201100024
ISSN:
14394227
e-ISSN:
14397633
Research Areas
Cancer
Environmental
Genetics And Genomics