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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Research Tales from the Clardy Laboratory: Function-Driven Natural Product Discovery

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Author(s):
Fukuda, Taise T. H. [1, 2] ; Cassilly, Chelsi D. [2] ; Gerdt, Joseph P. [3] ; Henke, Matthew T. [2] ; Helfrich, Eric J. N. [2] ; Mevers, Emily [2]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Dept Ciencias Farmaceut, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 - USA
[3] Indiana Univ, Dept Chem, Bloomington, IN 47405 - USA
Total Affiliations: 3
Document type: Review article
Source: Journal of Natural Products; v. 83, n. 3, SI, p. 744-755, MAR 27 2020.
Web of Science Citations: 0
Abstract

Over the past 70 years, the search for small molecules from nature has transformed biomedical research: natural products are the basis for half of all pharmaceuticals; the quest for total synthesis of natural products fueled development of methodologies for organic synthesis; and their biosynthesis presented unprecedented biochemical transformations, expanding our chemo-enzymatic toolkit. Initially, the discovery of small molecules was driven by bioactivity-guided fractionation. However, this approach yielded the frequent rediscovery of already known metabolites. As a result, focus shifted to identifying novel scaffolds through either structure-first methods or genome mining, relegating function as a secondary concern. Over the past two decades, the laboratory of Jon Clardy has taken an alternative route and focused on an ecology-driven, function-first approach in pursuit of uncovering bacterial small molecules with biological activity. In this review, we highlight several examples that showcase this ecology-first approach. Though the highlighted systems are diverse, unifying themes are (1) to understand how microbes interact with their host or environment, (2) to gain insights into the environmental roles of microbial metabolites, and (3) to explore pharmaceutical potential from these ecologically relevant metabolites. (AU)

FAPESP's process: 15/26349-5 - Chemical and ecological study of microorganisms associated with the symbiosis Cecropia-Azteca
Grantee:Taise Tomie Hebihara Fukuda
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 13/50954-0 - Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates
Grantee:Mônica Tallarico Pupo
Support type: BIOTA-FAPESP Program - Thematic Grants