Journal ArticleDOI
Microbial natural products: molecular blueprints for antitumor drugs
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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.read more
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Natural product discovery: past, present, and future
Leonard Katz,Richard H. Baltz +1 more
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.
Journal ArticleDOI
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.
Janette V. Pham,Mariamawit A. Yilma,Adriana Feliz,Murtadha T. Majid,Nicholas Maffetone,Jorge R. Walker,Eunji Kim,Hyo Je Cho,Jared M. Reynolds,Myoung Chong Song,Sung Ryeol Park,Sung Ryeol Park,Yeo Joon Yoon +12 more
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.
David J. Newman,Gordon M. Cragg +1 more
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
Next Generation Sequencing in Predicting Gene Function in Podophyllotoxin Biosynthesis
Joaquim V. Marques,Kye-Won Kim,Choonseok Lee,Michael A. Costa,Gregory D. May,John A. Crow,Laurence B. Davin,Norman G. Lewis +7 more
TL;DR: Regio-specific methylenedioxy bridge-forming CyP450s were identified catalyzing pluviatolide formation and this overall strategy enabled facile further identification of enzymes putatively involved in (−)-podophyllotoxin biosynthesis and underscores the deductive power of next generation sequencing and bioinformatics to probe and deduce medicinal plant biosynthetic pathways.
Journal ArticleDOI
Rare earth elements activate the secondary metabolite-biosynthetic gene clusters in Streptomyces coelicolor A3(2)
TL;DR: The rare earth elements, scandium and/or lanthanum, markedly activate, ranging from 2.5- to 12-fold, the expression of nine genes belonging to nine secondary metabolite–biosynthetic gene clusters of Streptomyces coelicolor A3(2) when added to the medium at low concentrations.
Journal ArticleDOI
Phase II trial of dolastatin-10 in patients with advanced breast cancer.
Edith A. Perez,David W. Hillman,Paul A. S. Fishkin,James E. Krook,Winston Tan,Phillip A. Kuriakose,Steven R. Alberts,Shaker R. Dakhil +7 more
TL;DR: The toxicity profile of dolastatin-10 was acceptable, it had minimal activity in this advanced breast cancer study, and it is decided not to pursue further clinical trials of this agent in the setting ofAdvanced breast cancer.
Journal ArticleDOI
A survey of nonribosomal peptide synthetase (NRPS) genes in Aspergillus nidulans
TL;DR: The genome of Aspergillus nidulans carries 27 genes encoding nonribosomal peptide synthetase (NRPS) structures, although only five of these forming peptides and amino acid containing metabolites have been identified so far.
Journal ArticleDOI
Bacterial production of the tunicate-derived antitumor cyclic depsipeptide didemnin B.
Moriya Tsukimoto,Masato Nagaoka,Yoshiyuki Shishido,Junji Fujimoto,Fukiko Nishisaka,Sachiko Matsumoto,Enjuro Harunari,Chiaki Imada,Takeshi Matsuzaki +8 more
TL;DR: It is reported that didemnin B, a tunicate-derived depsipeptide, has been isolated from a culturable bacterium, Tistrella mobilis YIT 12409.
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