Time filter

Source Type

Midway, KY, United States

Midway College is an independent, liberal arts college with approximately 1,800 students located in Midway, Kentucky. Related by covenant to the Christian Church , it currently offers two and four-year degrees. Midway is the only women's college in Kentucky. The all-female Day College offers majors in four pillar programs: business, equine studies, nursing, and teacher education.In addition to the Day College, Midway College offers programs to adult men and women, through the evening and weekend School for Career Development , offered on the Midway Campus and in more than 18 sites across Kentucky, and also through Midway College ONLINE. Both SCD and ONLINE offer accelerated degree-completion programs for working adults in popular programs such as Organizational Administration and Leadership, Homeland Security Corporate Management and Assessment, and Teacher Education, among others.In August 2011, Midway delayed the of launch of the new School of Pharmacy in the eastern Kentucky community of Paintsville. The school was supposed to enroll up to 80 students a year and intended to offer a fully accredited Pharm.D. degree. The School of Pharmacy was to occupy space at Big Sandy Community and Technical College while it seeks a site for its own campus.The mission of Midway College: "As Kentucky's only college for Women and as a forerunner in coeducational adult accelerated learning, Midway College empowers undergraduate and graduate students as leaders through a professionally-oriented liberal arts education." Wikipedia.

Kharel M.K.,Midway College | Rohr J.,University of Kentucky
Current Opinion in Chemical Biology | Year: 2012

The exact sequence of events in biosyntheses of natural products is essential not only to understand and learn from nature's strategies and tricks to assemble complex natural products, but also for yield optimization of desired natural products, and for pathway engineering and muta-synthetic preparation of analogues of bioactive natural products. Biosyntheses of natural products were classically studied applying in vivo experiments, usually by combining incorporation experiments with stable-isotope labeled precursors with cross-feeding experiments of putative intermediates. Later genetic studies were dominant, which consist of gene cluster determination and analysis of gene inactivation experiments. From such studies various biosynthetic pathways were proposed, to a large extent just through in silico analyses of the biosynthetic gene clusters after DNA sequencing. Investigations of the complex biosyntheses of the angucycline group anticancer drugs landomycin, jadomycin and gilvocarcin revealed that in vivo and in silico studies were insufficient to delineate the true biosynthetic sequence of events. Neither was it possible to unambiguously assign enzyme activities, especially where multiple functional enzymes were involved. However, many of the intriguing ambiguities could be solved after in vitro reconstitution of major segments of these pathways, and subsequent systematic variations of the used enzyme mixtures. This method has been recently termed 'combinatorial biosynthetic enzymology'. © 2012 Elsevier Ltd.

Pahari P.,University of Kentucky | Kharel M.K.,University of Kentucky | Kharel M.K.,Midway College | Shepherd M.D.,University of Kentucky | And 3 more authors.
Angewandte Chemie - International Edition | Year: 2012

Teamwork: Defucogilvocarcin M (1, see scheme) was synthesized in a one-pot, enzymatic reaction from acetyl-CoA and malonyl-CoA by a combination of 15 enzymes obtained from E. coli as well as the gilvocarcin, jadomycin, and ravidomycin biosynthetic pathways. The mixture of enzymes was systematically reduced and varied to further delineate the sequence of reactions in the complex, post-polyketide steps of gilvocarcin biosynthesis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kharel M.K.,University of Kentucky | Kharel M.K.,Midway College | Pahari P.,University of Kentucky | Shaaban K.A.,University of Kentucky | And 3 more authors.
Organic and Biomolecular Chemistry | Year: 2012

The functional roles of all proposed enzymes involved in the post-PKS redox reactions of the biosynthesis of various landomycin aglycones were thoroughly studied, both in vivo and in vitro. The results revealed that LanM2 acts as a dehydratase and is responsible for concomitant release of the last PKS-tethered intermediate to yield prejadomycin (10). Prejadomycin (10) was confirmed to be a general pathway intermediate of the biosynthesis. Oxygenase LanE and the reductase LanV are sufficient to convert 10 into 11-deoxylandomycinone (5) in the presence of NADH. LanZ4 is a reductase providing reduced flavin (FMNH) co-factor to the partner enzyme LanZ5, which controls all remaining steps. LanZ5, a bifunctional oxygenase-dehydratase, is a key enzyme directing landomycin biosynthesis. It catalyzes hydroxylation at the 11-position preferentially only after the first glycosylation step, and requires the presence of LanZ4. In the absence of such a glycosylation, LanZ5 catalyzes C5,6-dehydration, leading to the production of anhydrolandomycinone (8) or tetrangulol (9). The overall results provided a revised pathway for the biosynthesis of the four aglycones that are found in various congeners of the landomycin group. This journal is © 2012 The Royal Society of Chemistry.

Eric Nybo S.,University of Kentucky | Shabaan K.A.,University of Kentucky | Kharel M.K.,Midway College | Sutardjo H.,University of Kentucky | And 3 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2012

A new tetracenomycin analog, 8-demethyl-8-(4′-keto)-α-l- olivosyl-tetracenomycin C, was generated through combinatorial biosynthesis. Streptomyces lividans TK 24 (cos16F4) was used as a host for expression of a 'sugar plasmid' (pKOL) directing the biosynthesis of NDP-4-keto-l-olivose. This strain harbors all of the genes necessary for production of 8-demethyl- tetracenomycin C and the sugar flexible glycosyltransferase ElmGT. To the best of our knowledge, this report represents the first characterization of a tetracenomycin derivative decorated with a ketosugar moiety. Also, as far as we know, 4-keto-l-olivose has only been described as an intermediate of oleandomycin biosynthesis, but has not been described before as an appendage for a polyketide compound. Furthermore, this report gives further insight into the substrate flexibility of ElmGT to include an NDP-ketosugar, which is unusual and is rarely observed among glycosyltransferases from antibiotic biosynthetic pathways. © 2011 Elsevier Ltd. All rights reserved.

Noinaj N.,U.S. National Institutes of Health | Bosserman M.A.,University of Kentucky | Schickli M.A.,University of Kentucky | Piszczek G.,U.S. National Institutes of Health | And 5 more authors.
Journal of Biological Chemistry | Year: 2011

GilR is a recently identified oxidoreductase that catalyzes the terminal step of gilvocarcin V biosynthesis and is a unique enzyme that establishes the lactone core of the polyketide-derived gilvocarcin chromophore. Gilvocarcin-type compounds form a small distinct family of anticancer agents that are involved in both photo-activated DNA-alkylation and histone H3 cross-linking. High resolution crystal structures of apoGilR and GilR in complex with its substrate pregilvocarcin V reveals that GilR belongs to the small group of a relatively new type of the vanillyl-alcohol oxidase flavoprotein family characterized by bicovalently tethered cofactors. GilR was found as a dimer, with the bicovalently attached FAD cofactor mediated through His-65 and Cys-125. Subsequent mutagenesis and functional assays indicate that Tyr-445 may be involved in reaction catalysis and in mediating the covalent attachment of FAD, whereas Tyr-448 serves as an essential residue initiating the catalysis by swinging away from the active site to accommodate binding of the 6R-configured substrate and consequently abstracting the proton of the hydroxyl residue of the substrate hemiacetal 6-OH group. These studies lay the groundwork for future enzyme engineering to broaden the substrate specificity of this bottle-neck enzyme of the gilvocarcin biosynthetic pathway for the development of novel anti-cancer therapeutics.

Discover hidden collaborations