Molecular genetic and enzymological techniques have been employed to study antibiotic biosynthesis. The nonproteinogenic amino acid capreomycidine is the signature residue found in the tuberactinomycin family of antitubercular peptide antibiotics and an important element of the pharmacophore. Recombinant VioG, a single module peptide synthetase from the viomycin gene cluster cloned...
The isoprenoid pathway is one of the major biosynthetic pathways of secondary metabolites. Isoprenoids with a C₂₀ skeleton are known as diterpenoids and are derived from the common precursor, geranylgeranyl diphosphate (GGPP). This dissertation describes approaches to discover the diterpene synthase enzymes which provide the backbone structures for pleuromutilin and...
A gene cluster responsible for the biosynthesis of the antitumor agent
cetoniacytone A was identified in Actinomyces sp. strain Lu 9419, an
endosymbiotic bacteria isolated from the intestines of the rose chafer beetle. The
nucleotide sequence analysis of the 26 Kb DNA region revealed the presence of 17
complete ORFs,...
COUP-TFI, an orphan nuclear receptor of the steroid/thyroid hormone receptor superfamily, plays important roles in homeostasis and the CNS development, including differentiation, patterning, axonal projection, cell migration, cortical arealization and the temporal specification of neural stem cells. A number of COUP-interacting proteins have been described previously, and the majority of...
Metagenomics has revealed that the marine microbial biosphere is immensely more diverse than originally considered, and is an almost untapped reservoir for the potential discovery of microbial natural products. Despite numerous advances in culturing, biosynthetic engineering and genomic-based screening efforts to uncover much of this diversity in relatively accessible environments,...
Coibamide A is a highly methylated cyclic depsipeptide isolated from Panamanian marine filamentous cyanobacteria as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. This structurally unique agent exhibits potent cancer cell toxicity with an unprecedented selectivity profile in the National Cancer Institute (NCI) 60 cell line...
Cyclic nitramines are a class of compounds that include most of the commonly used explosives today. These are among the most common toxicants released into the environment as a result of human activity, generated on military ranges, battlefields, and production sites. Of these, hexahydro-1,3,5-trinitro-1,3,5- triazine (RDX) is of particular interest,...
Gadusol is a UV-B-absorbent compound found in fish and other marine organisms where it is presumed to play a role as a sunscreen and antioxidant. In light of commercial potential as a replacement for problematic synthetic sunscreens, a process to produce recombinant gadusol in the yeast Saccharomcyces cerevisiae was investigated....
The function of a protein is defined by its three-dimensional structure, and in understanding the three-dimensional structure of a protein, we gain an understanding of its function and mechanism. Protein structures, especially at high resolution, can provide detailed insights into many elements of enzyme function and catalysis – identifying residues...
The first part of this manuscript is about the total synthesis of the aspidosperma alkaloids leuconoxine, melodinine E and mersicarpine. Our synthetic strategy used a radical translocation-conjugate addition cascade to construct the core of the natural product. Specifically, a vinyl radical was generated from the homolysis of the C–I bond...