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Biosynthesis of Dolastatin 10 in Marine Cyanobacteria, a Prototype for Multiple Approved Cancer Drugs.
Kallifidas, Dimitris; Dhakal, Dipesh; Chen, Manyun; Chen, Qi-Yin; Kokkaliari, Sofia; Colon Rosa, Nicole A; Ratnayake, Ranjala; Bruner, Steven D; Paul, Valerie J; Ding, Yousong; Luesch, Hendrik.
Afiliação
  • Kallifidas D; Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida 32610, United States.
  • Dhakal D; Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida 32610, United States.
  • Chen M; Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida 32610, United States.
  • Chen QY; Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida 32610, United States.
  • Kokkaliari S; Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida 32610, United States.
  • Colon Rosa NA; Department of Chemistry, University of Florida, Gainesville, Florida 32611, United States.
  • Ratnayake R; Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida 32610, United States.
  • Bruner SD; Department of Chemistry, University of Florida, Gainesville, Florida 32611, United States.
  • Paul VJ; Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida 32610, United States.
  • Ding Y; Smithsonian Marine Station, Fort Pierce, Florida 34949, United States.
  • Luesch H; Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida 32610, United States.
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.
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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
Texto completo
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XML
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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