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

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.

SUBMITTER: Kallifidas D 

PROVIDER: S-EPMC10915760 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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

Kallifidas Dimitris D   Dhakal Dipesh D   Chen Manyun M   Chen Qi-Yin QY   Kokkaliari Sofia S   Colon Rosa Nicole A NA   Ratnayake Ranjala R   Bruner Steven D SD   Paul Valerie J VJ   Ding Yousong Y   Luesch Hendrik H  

Organic letters 20240208 7

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 <i>Caldora penicillata</i> 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 character  ...[more]

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