Research Tales from the Clardy Laboratory: Function-Driven Natural Product Discovery.
J Nat Prod
; 83(3): 744-755, 2020 03 27.
Article
em En
| MEDLINE
| ID: mdl-32105475
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bactérias
/
Produtos Biológicos
/
Descoberta de Drogas
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos