Nature Chemical Biology 5, 435 (2009). doi:10.1038/nchembio0709-435

Identifying and increasing access to the highest quality chemical probes will ensure their prominent position in the biological and drug discovery toolboxes.

Nature Chemical Biology 5, 448 (2009). doi:10.1038/nchembio.f.11

Authors: Stephen V Frye & Gary L Johnson

Small-molecule inhibitors can induce phosphorylation priming of AGC kinases. Priming by ATP binding pocket conformation, rather than intrinsic kinase activity, has significant implications for drug discovery and therapeutic efficacy.

Nature Chemical Biology 5, 450 (2009). doi:10.1038/nchembio0709-450

Author: Christian Hertweck

Microorganisms are a major source of new therapeutics. However, the discovery and sustainable production of these compounds are often hampered owing to limited access to biosynthetic genes or products. Recent studies provide new approaches for targeting biosynthesis genes in the metagenome of complex microbial assemblages and for inducing the expression of otherwise silent biosynthesis genes.

Nature Chemical Biology 5, 452 (2009). doi:10.1038/nchembio0709-452

Authors: Dario Neri & André W Brändli

A new methodology combining small molecules and phage-displayed peptides enables the isolation of chemically modified bicyclic peptides capable of high-affinity recognition of target proteins.

Nature Chemical Biology 5, 454 (2009). doi:10.1038/nchembio0709-454

Author: John A Gerlt

Westheimer's classical proposal that the decreased pKa of Lys115 in the active site of acetoacetate decarboxylase is the result of its unfavorable electrostatic juxtaposition with Lys116 has been evaluated by X-ray crystallography. The long-awaited structure reveals that Lys115 is positioned in a hydrophobic pocket that lowers its pKa.

Green fluorescent proteins are light-induced electron donors

Nature Chemical Biology 5, 459 (2009). doi:10.1038/nchembio.174

Authors: Alexey M Bogdanov, Alexander S Mishin, Ilia V Yampolsky, Vsevolod V Belousov, Dmitriy M Chudakov, Fedor V Subach, Vladislav V Verkhusha, Sergey Lukyanov & Konstantin A Lukyanov

Proteins of the green fluorescent protein (GFP) family are well known owing to their unique biochemistry and extensive use as in vivo markers. We discovered that GFPs of diverse origins can act as light-induced electron donors in photochemical reactions with various electron acceptors, including biologically relevant ones. Moreover, via green-to-red GFP photoconversion, this process can be observed in living cells without additional treatment.

Chromatin-level regulation of biosynthetic gene clusters

Nature Chemical Biology 5, 462 (2009). doi:10.1038/nchembio.177

Authors: Jin Woo Bok, Yi-Ming Chiang, Edyta Szewczyk, Yazmid Reyes-Domingez, Ashley D Davidson, James F Sanchez, Hsien-Chun Lo, Kenji Watanabe, Joseph Strauss, Berl R Oakley, Clay C C Wang & Nancy P Keller

Loss-of-function Aspergillus nidulans CclA, a Bre2 ortholog involved in histone H3 lysine 4 methylation, activated the expression of cryptic secondary metabolite clusters in A. nidulans. One new cluster generated monodictyphenone, emodin and emodin derivatives, whereas a second encoded two anti-osteoporosis polyketides, F9775A and F9775B. Modification of the chromatin landscape in fungal secondary metabolite clusters allows for a simple technological means to express silent fungal secondary metabolite gene clusters.

Identification of the toxic trigger in mushroom poisoning

Nature Chemical Biology 5, 465 (2009). doi:10.1038/nchembio.179

Authors: Masanori Matsuura, Yoko Saikawa, Kosei Inui, Koichi Nakae, Masayuki Igarashi, Kimiko Hashimoto & Masaya Nakata

We have isolated the small, highly strained carboxylic acid cycloprop-2-ene carboxylic acid from the Asian toxic mushroom Russula subnigricans. This compound is responsible for fatal rhabdomyolysis, a new type of mushroom poisoning that is indicated by an increase in serum creatine phosphokinase activity in mice. We found that polymerization of the compound at high concentrations via ene reaction abolishes its toxicity.