24 November, 2008
Volume 15, Issue 11
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Volume 15, Issue 11
On the cover: The bryostatins are polyketide natural products with potent anticancer and neurological activity isolated from the marine bryozoan, Bugula neritina. Recent studies have shown that these compounds are most likely produced by the uncultured symbiont “Candidatus Endobugula sertula,” and the polyketide synthase (PKS) gene cluster putatively responsible for prescribing the biosynthesis of bryostatin, bry, has recently been sequenced. In the study by Lopanik et al. (pp. 1175–1186), BryP, the trans-acyltransferase (AT) domain associated with bry, was shown to partially restore secondary metabolite production in vivo in a heterologous AT-deletion mutant. Complementary biochemical experiments demonstrated that BryP is able to load Co-bound extender units onto a variety of acyl carrier proteins and, more importantly, onto both native bry and heterologous PKS modules. The reported studies demonstrate the potential for pursuing in vitro studies on a microbial symbiont-derived biosynthetic pathway, in which a genetic system does not exist. These studies represent a key step in overcoming a decade-long barrier toward our goal of demonstrating indisputably that bry is responsible for specifying assembly of the bryostatins.
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Reviews in Chemistry & Biology
- Brian C. Smith, William C. Hallows and John M. Denu
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- M. Wang and C. Fotsch
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In the November Issue
Innovations: Food and Drugs...
In Mini-review: Psssst, Bacteria are Talking
In Brief: Modulating Intrinsic Disorder
Protein-Protein Interactions within the Type II PKS Complex
Cover Story: Microbial Symbiont Investigated
Genetically Encoding Nε -(o-Azidobenzyloxycarbonyl)lysine
Improved Anti-Fungal Polyene Macrolides
Structural Requirements for Cannabinoid Receptor Binding
Featured Article
Featured articles are freely available to all readers
- Taek Jin Kang, Satoshi Yuzawa, and Hiroaki Suga
By redefining the genetic code, one can make the ribosome incorporate non-proteinogenic amino acids into peptides according to information encoded in mRNAs. Using this genetic code reprogramming, Kang et al. have prepared a series of N-terminal tails of histone H3 containing combinatorial lysine modifications, including mono-, di-, and tri-methylation and acetylation. The full-length 38-mer H3 tails with distal combinatorial modification enabled Kang et al. to reveal the possible crosstalk among epigenetic markers upon HP1 chromodomain binding. (Figure provided by Kang et al.)
New Articles
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Psssst, Bacteria are Talking Minireview by Cooley et al. discusses the most recent findings that some soild bacteria have the ability to employ host-derived compounds and produce alternative N-acylhomoserine lactones. Additionally, article also discusses the recently described mechanism of how once of N-acylhomoserine lactones affects host inflammatory signaling pathways to promote bacterial survival. |
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Modulating Intrinsic Disorder Follis et al. describe the interactions of two small molecules that form soluble, reversible complexes with c-Myc. These findings suggest that potential binding sites may be prevalent in intrinsically disordered proteins and that the discovery of small molecules capable of modulating the functions of these proteins may be practicable. |
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Anti-Fungal Polyene Macrolides Efficient and safe anti-fungal agents are urgently needed due to the growing number of life-threatening systemic fungal infections. Brautaset et al. generated analogues of the polyene macrolide antibiotic, nystatin, using biosynthetic engineering, and tested the obtained compounds for anti-fungal activity and toxicity both in vitro and in vivo, with promising results. |
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Isoform Specific Activators of AMPK The thienopyridone drug A769662 has been shown to activate AMP-activated protein kinase (AMPK) by an AMP-independent mechanism. Scott et al. now demonstrate that A769662 selectively activates specific isoforms of AMPK, highlighting the feasability of developing isoform specific activators of AMPK that can target AMPK in particular tissues. |
