The cyanobactin biosynthetic machinery: promiscuity, modularity and unique chemistry from the oceans

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Title The cyanobactin biosynthetic machinery: promiscuity, modularity and unique chemistry from the oceans
Publication Type dissertation
School or College College of Pharmacy
Department Medicinal Chemistry
Author Sardar, Debosmita
Date 2016
Description Cyanobactins are peptide natural products that fall under the broad class of the ribosomally synthesized and posttranslationally modified peptides (RiPPs). Since they are synthesized by the ribosome, the biosynthesis of these peptides is genetically encoded. A precursor peptide gene carries the primary amino acid sequence of the natural product. The precursor peptide is surrounded by other genes, which encode posttranslational enzymes that decorate the primary sequence with elaborate structural motifs. Due to the genetically encoded origins of the cyanobactins, simple manipulations at the peptide sequence level are tolerable and lead to the creation of a diversity of natural products. The roots to this tolerance lie in the innate extreme broad-substrate nature of the posttranslational enzymes. Here, we explore the biochemical basis of this promiscuity and in vitro methodologies to create structurally elaborate peptidic motifs. In addition, the cyanobactin biosynthetic machinery is a rich source of enzymes capable of performing a wide array of intriguing chemistry and here we probe into some of these mechanisms. Put together, the broad-substrate nature coupled with the unique enzymology of the cyanobactin biosynthetic machinery provides a toolkit for the creation of designer peptide motifs. This work holds promise in the field of peptide-based drug discovery.
Type Text
Publisher University of Utah
Subject Biochemistry
Dissertation Name Doctor of Philosophy
Language eng
Rights Management (c) Debosmita Sardar
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s64501mz
Setname ir_etd
ID 1419007
Reference URL https://collections.lib.utah.edu/ark:/87278/s64501mz
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