Biosynthesis of Dolastatin 10 in Marine Cyanobacteria, a Prototype for Multiple Approved Cancer Drugs.
Org Lett
; 26(7): 1321-1325, 2024 Feb 23.
Article
em En
| MEDLINE
| ID: mdl-38330916
ABSTRACT
Dolastatin 10, a potent tubulin-targeting marine anticancer natural product, provided the basis for the development of six FDA-approved antibody-drug conjugates. Through the screening of cyanobacterial Caldora penicillata environmental DNA libraries and metagenome sequencing, we identified its biosynthetic gene cluster. Functional prediction of 10 enzymes encoded in the 39 kb cluster supports the dolastatin 10 biosynthesis. The nonheme diiron monooxygenase DolJ was biochemically characterized to mediate the terminal thiazole formation in dolastatin 10.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cianobactérias
/
Depsipeptídeos
/
Neoplasias
/
Antineoplásicos
Idioma:
En
Revista:
Org Lett
Ano de publicação:
2024
Tipo de documento:
Article