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Biosynthesis of Dolastatin 10 in Marine Cyanobacteria, a Prototype for Multiple Approved Cancer Drugs.

Authors :
Kallifidas D
Dhakal D
Chen M
Chen QY
Kokkaliari S
Colon Rosa NA
Ratnayake R
Bruner SD
Paul VJ
Ding Y
Luesch H
Source :
Organic letters [Org Lett] 2024 Feb 23; Vol. 26 (7), pp. 1321-1325. Date of Electronic Publication: 2024 Feb 08.
Publication Year :
2024

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.

Details

Language :
English
ISSN :
1523-7052
Volume :
26
Issue :
7
Database :
MEDLINE
Journal :
Organic letters
Publication Type :
Academic Journal
Accession number :
38330916
Full Text :
https://doi.org/10.1021/acs.orglett.3c04083