EVidenceModeler (EVM) is presented as an automated eukaryotic gene structure annotation tool that reports eukaryotic gene structures as a weighted consensus of all available evidence. EVM, when combined with the Program to Assemble Spliced Alignments (PASA), yields a comprehensive, configurable annotation system that predicts protein-coding genes and alternatively spliced isoforms. Our experiments on both rice and human genome sequences demonstrate that EVM produces automated gene structure annotation approaching the quality of manual curation.

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Automated Eukaryotic Gene Structure Annotation Using EVidenceModeler and the Program to Assemble Spliced Alignments

ion from the Sugar Moiety Wendy Knapp Pogozelski† and Thomas D. Tullius*,‡ Department of Chemistry, State University of New York at Geneseo, Geneseo, New York 14454, and Department of Chemistry, Boston University, Boston, Massachusetts 02215 Received August 27, 1997 (Revised Manuscript Received February 26, 1998)

Oxidative Strand Scission of Nucleic Acids: Routes Initiated by Hydrogen Abstraction from the Sugar Moiety.

FeII/alpha-ketoglutarate (alphaKG)-dependent hydroxylases catalyze an amazing diversity of reactions that result in protein side-chain modifications, repair of alkylated DNA/RNA, biosynthesis of antibiotics and plant products, metabolism related to lipids, and biodegradation of a variety of compounds. These enzymes possess a beta-strand "jellyroll" structural fold that contains three metal-binding ligands found in a His1-X-Asp/Glu-Xn-His2 motif. The cosubstrate, alphaKG, chelates FeII using its C-2 keto group (binding opposite the Asp/Glu residue) and C-1 carboxylate (coordinating opposite either His1 or His2). Oxidative decomposition of alphaKG forms CO2 plus succinate and leads to the generation of an FeIV-oxo or other activated oxygen species that hydroxylate the primary substrate. The reactive oxygen species displays alternate reactivity in related enzymes that catalyze desaturations, ring expansions, or ring closures. Other enzymes resemble the FeII/alphaKG-dependent hydroxylases in terms of protein structure or chemical mechanism but do not utilize alphaKG as a substrate. This review describes the reactions catalyzed by this superfamily of enzymes, highlights key active site features revealed by structural studies, and summarizes results from spectroscopic and other approaches that provide insights into the chemical mechanisms.

FeII/alpha-ketoglutarate-dependent hydroxylases and related enzymes.

Genetic Contributions to Understanding Polyketide Synthases.

Chemistry and Biology of Mycotoxins and Related Fungal Metabolites

Species in the genus Cercospora cause economically devastating diseases in sugar beet, maize, rice, soy bean, and other major food crops. Here, we sequenced the genome of the sugar beet pathogen Cercospora beticola and found it encodes 63 putative secondary metabolite gene clusters, including the cercosporin toxin biosynthesis (CTB) cluster. We show that the CTB gene cluster has experienced multiple duplications and horizontal transfers across a spectrum of plant pathogenic fungi, including the wide-host range Colletotrichum genus as well as the rice pathogen Magnaporthe oryzae. Although cercosporin biosynthesis has been thought to rely on an eight-gene CTB cluster, our phylogenomic analysis revealed gene collinearity adjacent to the established cluster in all CTB cluster-harboring species. We demonstrate that the CTB cluster is larger than previously recognized and includes cercosporin facilitator protein, previously shown to be involved with cercosporin autoresistance, and four additional genes required for cercosporin biosynthesis, including the final pathway enzymes that install the unusual cercosporin methylenedioxy bridge. Lastly, we demonstrate production of cercosporin by Colletotrichum fioriniae, the first known cercosporin producer within this agriculturally important genus. Thus, our results provide insight into the intricate evolution and biology of a toxin critical to agriculture and broaden the production of cercosporin to another fungal genus containing many plant pathogens of important crops worldwide.

https://www.pnas.org/content/pnas/115/24/E5459.full.pdf

Gene cluster conservation provides insight into cercosporin biosynthesis and extends production to the genus Colletotrichum

Experiments and speculations on the role of oxidative cyclization chemistry in natural product biosynthesis

Purification and Characterization of Clavaminate Synthase from Streptomyces antibioticus: A MULTIFUNCTIONAL ENZYME OF CLAVAM BIOSYNTHESIS (∗)

A general strategy is described for the preparation of substituted xanthones and embodied in the preparation of (±)-O-methylsterigmatocystin (OMST), the most advanced, known intermediate in the bio...

Craig A. Townsend

Papers

Gene cluster conservation provides insight into cercosporin biosynthesis and extends production to the genus Colletotrichum

Experiments and speculations on the role of oxidative cyclization chemistry in natural product biosynthesis

Purification and Characterization of Clavaminate Synthase from Streptomyces antibioticus: A MULTIFUNCTIONAL ENZYME OF CLAVAM BIOSYNTHESIS (∗)

Total Synthesis of O-Methylsterigmatocystin Using N-Alkylnitrilium Salts and Carbonyl−Alkene Interconversion in a New Xanthone Synthesis

Nocardicin A: stereochemical and biomimetic studies of monocyclic β-lactam formation