Pericyclic reactions are among the most powerful synthetic transformations to make multiple regioselective and stereoselective carbon-carbon bonds1. These reactions have been widely applied for the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centers2–6. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples, intramolecular Diels-Alder (IMDA) reaction7, Cope8 and Claisen rearrangements9, have been characterized. Here, we report the discovery of a S-adenosyl-L-methionine (SAM) dependent enzyme LepI that can catalyse stereoselective dehydration, bifurcating IMDA/hetero-DA (HDA) reactions via an ambimodal transition state, and a [3,3]-sigmatropic retro-Claisen rearrangement leading to the formation of dihydopyran core in the fungal natural product leporin10. Combined in vitro enzymatic characterization and computational studies provide evidence and mechanistic insight about how the O-methyltransferase-like protein LepI regulates the bifurcating biosynthetic reaction pathways (“direct” HDA and “byproduct recycle” IMDA/retro-Claisen reaction pathways) by utilizing SAM as the cofactor in order to converge to the desired biosynthetic end product. This work highlights that LepI is the first example of an enzyme catalysing a (SAM-dependent) retro-Claisen rearrangement. We suggest that more pericyclic biosynthetic enzymatic transformations are yet to be discovered in the intriguing enzyme toolboxes in Nature11, and propose an ever expanding role of the versatile cofactor SAM in enzyme catalysis.

Communications cut-off filters (RG 610 nm for PtOEP, OG 590 nm for [Ru(4,,]CI2) were placed in front of a liquid-nitrogen cooled CCD detector (Model LN/CCD, Princeton Instruments, Inc.), with 578 x 384 pixels in a cell size of 13.25 x 8.83 mm'. Luminescent light from the sample surface was collected with a camera lens (Nikon, 55 mm, 1:1.2) and an imaged formed on the CCD camera. The pressure of the sample chamber was measured using a pressure gauge (Model FA 233, Wallace & Tiernan) with an accuracy of 5 0.1 psi.Trichloroethane was used as the solvent to dissolve the dyes and the polymer 3. The dye concentration in the polymer matrixes ranged from 10 to 1000 ppm. Solutions containing the dye and polymer were spray coated onto the surface of interest. Some of the surfaces were precoated with an epoxy primer of a two-part system based on Super One-Coatm White D3400 and Glass Activator D3498 supplied by Pratt & Lambert. The dye film itself was very thin (between 5 and 15 pm) except for the measurements shown in [*] Prof.

A warm-white light-emitting diode (LED) without blending of different kinds of phosphors is demonstrated. An approach that consists of a blue LED chip and a wavelength-conversion phosphor is carried out. The phosphor is a newly developed yellowish orange CaEuSiAlON ceramic phosphor with high efficiency. The CIE1931 chromaticity coordinates (x, y) are (0.458, 0.414), the color temperature is 2750 K, and the luminous efficacy of this LED is 25.9 lm/W at room temperature and with a forward-bias current of 20 mA. The chromaticity of the assembled LED is more thermally stable than that of a LED with a conventional oxide phosphor (YAG:Ce) because of the better thermal stability of the oxynitride phosphor.

Wc studied the role of non.selecttv© tyi~ (ET.) of ¢ndothelin (ET} receptor in the vaseulature, using a ligand specific to the fiT. receptor) [Olu~] • sarafotoxin S6b ([Olu'*lgR'rh}. Endothelium.containln8 rat thoracic aorta pos~s~d specific binding sites For ~)l.[OhP]SRTb. which were almost diminatcd by removal ctf the endothelium, while ET.3-sl~cific binding sites were not detected in tl' c endothdium.intaet rat aorl=. Only ET, receptor was deIected in the membranes From the endothdium of porcine thoracic aorta. [GIu'~ISR.Tb exerted only vasodilalion in rat aortic rinB. These findings indicate that El?. receptors are located on vascular endothellum and linked to vasodilation.

Diels-Alder reactions are among the most powerful synthetic transformations to construct complex natural products. Despite that increasing of enzymatic intramolecular Diels-Alder reactions have been discovered, natural intermolecular Diels-Alderases are rarely described. Here, we report an intermolecular hetero-Diels-Alder reaction in the biosynthesis of tropolonic sesquiterpenes and functionally characterize EupfF as the first fungal intermolecular hetero-Diels-Alderase. We demonstrate that EupfF catalyzed the dehydration of a hydroxymethyl-containing tropolone (5) to generate a reactive tropolone o-quinone methide (6) and might further *

The pericyclases are a growing superfamily of enzymes that catalyze pericyclic reactions. We report a pericyclase IccD catalyzing an inverse-electron demand Diels-Alder (IEDDA) reaction with a rate acceleration of 3 × 10 5 fold in the biosynthesis of fungal natural product ilicicolin H. We demonstrate IccD is highly periselective towards the IEDDA cycloaddition over a competing normal electron demand Diels-Alder (NEDDA) reaction from an ambimodal transition state. A predicted flavoenzyme IccE was identified to epimerize the IEDDA product 8-epi-ilicicolin H to ilicicolin H, a step that is critical for the observed antifungal activity of ilicicolin H. Our results reveal the ilicicolin H biosynthetic pathway and add to the collection of pericyclic reactions that are catalyzed by pericyclases.

The pericyclases are Nature's route to spirotetronates, statins, myceliothermophins, leporins and more.

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