Catalyzed Reactions of Organosiliconhydrides with α, β Unsaturated Ketones

The addition of organosiliconhydrides to olefins has been of laboratory and industrial importance for twenty-five years. Literally hundreds of examples may be cited describing reactions of organosilicon­hydrides with a wide spectrum of olefinic compounds. These reactions have been conducted in either the catalyzed or uncatalyzed state. While the reactions may be forced under the influence of heat and pressure, they are more economically and practically carried out in the presence of catalysts. Catalysts encompass a wide variety of materials including peroxides, tertiary bases, metals, metal salts, U.V light, and gamma radiation

Structure in the 3D Galaxy Distribution: I. Methods and Example Results

Three methods for detecting and characterizing structure in point data, such as that generated by redshift surveys, are described: classification using self-organizing maps, segmentation using Bayesian blocks, and density estimation using adaptive kernels. The first two methods are new, and allow detection and characterization of structures of arbitrary shape and at a wide range of spatial scales. These methods should elucidate not only clusters, but also the more distributed, wide-ranging filaments and sheets, and further allow the possibility of detecting and characterizing an even broader class of shapes. The methods are demonstrated and compared in application to three data sets: a carefully selected volume-limited sample from the Sloan Digital Sky Survey redshift data, a similarly selected sample from the Millennium Simulation, and a set of points independently drawn from a uniform probability distribution -- a so-called Poisson distribution. We demonstrate a few of the many ways in which these methods elucidate large scale structure in the distribution of galaxies in the nearby Universe.Comment: Re-posted after referee corrections along with partially re-written introduction. 80 pages, 31 figures, ApJ in Press. For full sized figures please download from: http://astrophysics.arc.nasa.gov/~mway/lss1.pd

Microbial synthesis of antimalarial compound FR-900098: pathway characterization and engineering

Phosphonates represent a small, but potent group of compounds with many useful therapeutic properties. FR-900098 is a novel chemotherapeutic agent for the treatment of malaria and has been effective in humans and other animals. This compound inhibits 1-deoxy-D-xylulose-5-phosphate (DXP) reductoisomerase, the second step in the nonmevalonate pathway for isoprenoid biosynthesis for many organisms including Plasmodium falciparum, the parasite responsible for the most virulent form of the disease. The biosynthetic cluster for FR-900098 has recently been cloned from Streptomyces rubellomurinus and heterologously expressed in Streptomyces lividans and Escherichia coli. In this work, we sought to obtain complete elucidation of the FR-900098 biosynthetic pathway. Detailed biochemical studies with purified enzymes were used to verify each of the reactions in the antimalarial biosynthesis. In doing so, we revealed an unprecedented functional role for nucleotide conjugation to intermediates within the pathway. We also describe the characterization of one of the enzymes involved in FR-900098 biosynthesis, the FAD and NADPH dependent N-hydroxylase FrbG. A series of biochemical analyses and the solved crystal structure provided insights into the catalytic mechanism, including nucleotide conjugation as a recognition mechanism for FrbG activity. A thorough understanding of the FR-900098 biosynthetic pathway also provided a platform for directed biosynthesis to generate novel derivatives of the compound and metabolic engineering in E. coli to increase production of the antimalarial. Although not required for FR-900098 biosynthesis, the Fe(II) and ??-ketoglutarate dependent hydroxylase FrbJ was determined to be involved in the synthesis of another phosphonate antibiotic FR-33289. We demonstrated its ability to catalyze the hydroxylation of additional substrates as part of the creation of a new library of potential antimalarial compounds. Through a series of bioassays and in vitro experiments, we identified two new prospective antimalarials. Metabolic engineering to increase FR-900098 production in E. coli was approached in two ways, the first of which was the targeted increase of phosphoenolpyruvate (PEP) concentration within the cell. This metabolite is a common precursor of phosphonates and is also involved in several reactions of primary metabolism. The second approach was to balance flux through the FR-900098 biosynthetic pathway through ribosome binding site (rbs) engineering