Current Opinion in Chemical Biology

Current developments and challenges in the search for a naturally selected Diels-Alderase.

Publication Date: 2012 Jan 17 PMID: 22260931
Authors: Kim, H. J. - Ruszczycky, M. W. - Liu, H. W.
Journal: Curr Opin Chem Biol

Only a very few examples of enzymes known to catalyze pericyclic reactions have been reported, and presently no enzyme has been demonstrated unequivocally to catalyze a Diels-Alder reaction. Nevertheless, research into secondary metabolism has led to the discovery of numerous natural products exhibiting the structural hallmarks of [4+2] cycloadditions, prompting efforts to characterize the responsible enzymatic processes. These efforts have resulted in a growing collection of enzymes believed to catalyze pericyclic [4+2] cycloaddition reactions; however, in each case the complexity of the substrates and catalytic properties of these enzymes poses significant challenges in substantiating these hypotheses. Herein we consider the principles motivating these efforts and the enzymological systems currently under investigation.

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Novel applications of plant polyketide synthases.

Publication Date: 2012 Jan 13 PMID: 22245533
Authors: Abe, I.
Journal: Curr Opin Chem Biol

The structurally and mechanistically simple type III polyketide synthases (PKSs) catalyze iterative condensations of CoA thioesters to produce a variety of polyketide scaffolds with remarkably diverse structures and biological activities. By exploiting the enzymes, we combined precursor-directed biosynthesis with nitrogen-containing substrates and structure-based enzyme engineering and generated unnatural, novel polyketide-alkaloid scaffolds with promising biological activities. The nucleophilic nitrogen atom and the engineered enzymes thus facilitated the formation of additional CC and CN bonds during the enzymatic transformations. The methodology will contribute to the further production of chemically and structurally divergent, unnatural natural products, as well as the rational design of novel biocatalysts with unprecedented catalytic functions.

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Trends in ultrasensitive proteomics.

Publication Date: 2012 Jan 6 PMID: 22226769
Authors: Altelaar, A. M. - Heck, A. J.
Journal: Curr Opin Chem Biol

Here we review recent developments and trends in sample preparation, pre-fractionation, chromatography and mass spectrometry contributing towards the ultra-sensitive global analysis of proteins. Highly sensitive MS-based proteomics is not only beneficiary for the proteome analysis of single cells, an aim which is getting into reach, but also clearly relevant for the analysis of (a) subcellular organelles, (b) specific low-abundant cell-types such as adult stem cells, and (c) smaller but more homogeneous cell populations sorted or dissected from (diseased) tissue.

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