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Journal ArticleDOI

Microbial natural products: molecular blueprints for antitumor drugs

Lesley-Ann Giddings, +1 more
- 03 Sep 2013 - 
- Vol. 40, Iss: 11, pp 1181-1210
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TLDR
This review describes only a handful of exemplary natural products and their derivatives as well as those that have served as elegant blueprints for the development of novel synthetic structures that are either currently in use or in clinical or preclinical trials together with some of their earlier analogs in some cases whose failure to proceed aided in the derivation of later compounds.
Abstract
Microbes from two of the three domains of life, the Prokarya, and Eukarya, continue to serve as rich sources of structurally complex chemical scaffolds that have proven to be essential for the development of anticancer therapeutics. This review describes only a handful of exemplary natural products and their derivatives as well as those that have served as elegant blueprints for the development of novel synthetic structures that are either currently in use or in clinical or preclinical trials together with some of their earlier analogs in some cases whose failure to proceed aided in the derivation of later compounds. In every case, a microbe has been either identified as the producer of secondary metabolites or speculated to be involved in the production via symbiotic associations. Finally, rapidly evolving next-generation sequencing technologies have led to the increasing availability of microbial genomes. Relevant examples of genome mining and genetic manipulation are discussed, demonstrating that we have only barely scratched the surface with regards to harnessing the potential of microbes as sources of new pharmaceutical leads/agents or biological probes.

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Citations
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Journal ArticleDOI

Natural product discovery: past, present, and future

TL;DR: Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.
Journal Article

Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization.:II. FERMENTATION, ISOLATION AND CHARACTERIZATION

TL;DR: Rapamycin is a new antifungal antibiotic produced by Streptomyces hygroscopicus and can be classified as a triene, highly active against various Candida species, especially Candida albicans.
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Metabolite induction via microorganism co-culture: A potential way to enhance chemical diversity for drug discovery

TL;DR: Co-culture studies that aim to increase the diversity of metabolites obtained from microbes, with a special emphasis on the multiple methods of performing co-culture experiments, are focused on.
Journal ArticleDOI

A Review of the Microbial Production of Bioactive Natural Products and Biologics.

TL;DR: The structures and diverse biological activities of natural products and recombinant proteins that have been exploited as valuable molecules in medicine, agriculture and insect control are introduced and suggested to inspire the development of new therapeutic agents in academia and industry.
Journal ArticleDOI

Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development.

TL;DR: This review shows the compounds derived from marine sources that are currently in clinical trials against cancer and the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies.
References
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Journal ArticleDOI

Kahalalides: Bioactive Peptides from a Marine Mollusk Elysia rufescens and Its Algal Diet Bryopsis sp.(1).

TL;DR: Six new peptides are described, including kahalalide F, which are cyclic depsipeptides, ranging from a C(31) tripeptide to aC(75) tridecapeptide isolated from a sacoglossan mollusk, Elysiarufescens.
Journal ArticleDOI

Total synthesis of the potent proteasome inhibitor epoxomicin: a useful tool for understanding proteasome biology.

TL;DR: The first syntheses of epoxomicin, [3H]-epoxomalin, and a biotinylated ep oxomicin analog as well as the absolute configuration of the epoxide stereocenter are reported.
Journal Article

New strategies for drug discovery: Activation of silent or weakly expressed microbial gene clusters

TL;DR: Current progress on activation of silent genes, utilization of “natural” mutant-type RNA polymerases and rare earth elements, and the applicability of ribosome engineering to myxobacteria and fungi are reviewed.
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