Natural product discovery and engineering at the protein, pathway, and genome scales
type: CreativeWork
description: For centuries, mankind has turned to natural sources for cures, remedies, and ways to improve its quality of life. It was not until the discovery of the antibiotic penicillin in 1928, however, that natural products – small molecule secondary metabolites produced by a variety of organisms for a variety of purposes – were truly appreciated as the source of these beneficial properties. In the ensuing decades, research in the field of natural products boomed, and a number of discoveries were made that revolutionized global health. In the 1970s and 1980s, however, these discoveries started to become fewer and farther between, prompting pharmaceutical companies to turn away from natural products research in favor of synthetic chemistry approaches to drug discovery. Nevertheless, despite diminishing returns from traditional natural product discovery methods, modern genomics has in fact revealed that vast numbers of natural product gene clusters exist across all domains of life, far in excess of the number of known natural products and far surpassing any previous predictions. Thus, natural product discovery efforts to date have only scratched the surface of Nature’s true capabilities. In this work, we sought to leverage modern techniques for natural product discovery at the protein, pathway, and genome scales to tap into this biosynthetic potential. The past several years have seen the development of many tools for the manipulation of DNA with ease and precision far exceeding the standards set by traditional methods. These methods, combined with the ever-increasing number of putative natural product pathways revealed by genome sequencing efforts, open the door for new platforms of natural product discovery and engineering. At the protein level, we demonstrate the synthesis of novel derivatives of the antimalarial natural product FR-900098 by leveraging the substrate promiscuity of the native biosynthetic machinery. Through structural and biochemical characterization of the …
abstract: For centuries, mankind has turned to natural sources for cures, remedies, and ways to improve its quality of life. It was not until the discovery of the antibiotic penicillin in 1928, however, that natural products – small molecule secondary metabolites produced by a variety of organisms for a variety of purposes – were truly appreciated as the source of these beneficial properties. In the ensuing decades, research in the field of natural products boomed, and a number of discoveries were made that revolutionized global health. In the 1970s and 1980s, however, these discoveries started to become fewer and farther between, prompting pharmaceutical companies to turn away from natural products research in favor of synthetic chemistry approaches to drug discovery. Nevertheless, despite diminishing returns from traditional natural product discovery methods, modern genomics has in fact revealed that vast numbers of natural product gene clusters exist across all domains of life, far in excess of the number of known natural products and far surpassing any previous predictions. Thus, natural product discovery efforts to date have only scratched the surface of Nature’s true capabilities. In this work, we sought to leverage modern techniques for natural product discovery at the protein, pathway, and genome scales to tap into this biosynthetic potential. The past several years have seen the development of many tools for the manipulation of DNA with ease and precision far exceeding the standards set by traditional methods. These methods, combined with the ever-increasing number of putative natural product pathways revealed by genome sequencing efforts, open the door for new platforms of natural product discovery and engineering. At the protein level, we demonstrate the synthesis of novel derivatives of the antimalarial natural product FR-900098 by leveraging the substrate promiscuity of the native biosynthetic machinery. Through structural and biochemical characterization of the …
author: Cobb, Ryan Ellis
language: en
keywords: natural products, FR-900098, FrbF, polyketide, phosphonic acid, Streptomyces, Clustered regularly interspaced short palindromic repeats (CRISPR), Cas9
date published: 2015-07-22T22:33:12Z
date modified: 2026-07-22T22:26:12Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/78600