Prospecting for natural products by genome mining and microcrystal electron diffraction.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
11
03
2021
accepted:
14
06
2021
entrez:
27
7
2021
pubmed:
28
7
2021
medline:
8
9
2021
Statut:
ppublish
Résumé
More than 60% of pharmaceuticals are related to natural products (NPs), chemicals produced by living organisms. Despite this, the rate of NP discovery has slowed over the past few decades. In many cases the rate-limiting step in NP discovery is structural characterization. Here we report the use of microcrystal electron diffraction (MicroED), an emerging cryogenic electron microscopy (CryoEM) method, in combination with genome mining to accelerate NP discovery and structural elucidation. As proof of principle we rapidly determine the structure of a new 2-pyridone NP, Py-469, and revise the structure of fischerin, an NP isolated more than 25 years ago, with potent cytotoxicity but hitherto ambiguous structural assignment. This study serves as a powerful demonstration of the synergy of MicroED and synthetic biology in NP discovery, technologies that when taken together will ultimately accelerate the rate at which new drugs are discovered.
Identifiants
pubmed: 34312563
doi: 10.1038/s41589-021-00834-2
pii: 10.1038/s41589-021-00834-2
pmc: PMC8447837
mid: NIHMS1738858
doi:
Substances chimiques
Biological Products
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
872-877Subventions
Organisme : NIAID NIH HHS
ID : R01 AI141481
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM128867
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
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