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
Didemnins: antiviral and antitumor depsipeptides from a caribbean tunicate
Kenneth L. Rinehart,James B. Gloer,R. G. Hughes,H. E. Renis,J. P. McGovren,E. B. Swynenberg,Dale A. Stringfellow,S. L. Kuentzel,L. H. Li +8 more
TL;DR: Extracts of samples of a Caribbean tunicate of the family Didemnidae inhibit in vitro at low concentrations the growth of DNA and RNA viruses as well as L1210 leukemic cells.
Journal ArticleDOI
Crystal structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of beta-lactone ring opening and a mechanism for irreversible binding.
TL;DR: The crystal structures of the yeast 20S proteasome core particle (CP) in complex with Salinosporamides A and B were solved and the collective data provide new insights into the mechanism of inhibition and irreversible binding of 1.
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Evidence for the Biosynthesis of Bryostatins by the Bacterial Symbiont “Candidatus Endobugula sertula” of the Bryozoan Bugula neritina
Seana K. Davidson,Seana K. Davidson,S. W. Allen,Grace E. Lim,Grace E. Lim,Christine Anderson,Christine Anderson,Margo G. Haygood,Margo G. Haygood +8 more
TL;DR: This study demonstrates that it may be possible to clone bryostatin genes from B. neritina directly and use these to produce brystatins in heterologous host bacteria.
Journal ArticleDOI
Development of Yondelis® (trabectedin, ET-743). A semisynthetic process solves the supply problem
Carmen Cuevas,Andrés Francesch +1 more
TL;DR: Ecteinascidins are marine natural products consisting of two or three linked tetrahydroisoquinoline subunits and an active carbinolamine functional group that make them attractive candidates for development as anticancer agents.
Journal ArticleDOI
Bryostatin, an activator of the calcium phospholipid-dependent protein kinase, blocks phorbol ester-induced differentiation of human promyelocytic leukemia cells HL-60
TL;DR: The research indicates that bryostatin, a macrocyclic lactone that binds to the phorbol ester receptor in human polymorphonuclear leukocytes, also binds to this receptor in the human promyelocytic leukemia cell line, HL-60, and suggests that some of the biologic effects of ph orbol esters may occur through a more complex mechanism than previously thought.
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