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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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]
Número total de Autores: 6
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 3
Tipo de documento: Artigo de Revisão
Fonte: Journal of Natural Products; v. 83, n. 3, SI, p. 744-755, MAR 27 2020.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 15/26349-5 - Estudo químico e ecológico de microrganismos associados à simbiose Cecropia-Azteca
Beneficiário:Taise Tomie Hebihara Fukuda
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 13/50954-0 - Novos agentes terapêuticos obtidos de bactérias simbiontes de invertebrados brasileiros
Beneficiário:Mônica Tallarico Pupo
Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático