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Giant polyketide synthase enzymes in the biosynthesis of giant marine polyether toxins.
Fallon, Timothy R; Shende, Vikram V; Wierzbicki, Igor H; Pendleton, Amanda L; Watervoort, Nathan F; Auber, Robert P; Gonzalez, David J; Wisecaver, Jennifer H; Moore, Bradley S.
Afiliación
  • Fallon TR; Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and University of California, San Diego, La Jolla, CA 92093, USA.
  • Shende VV; Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and University of California, San Diego, La Jolla, CA 92093, USA.
  • Wierzbicki IH; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Pendleton AL; Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
  • Watervoort NF; Purdue Center for Plant Biology, Purdue University, West Lafayette, IN 47907, USA.
  • Auber RP; Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
  • Gonzalez DJ; Purdue Center for Plant Biology, Purdue University, West Lafayette, IN 47907, USA.
  • Wisecaver JH; Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
  • Moore BS; Purdue Center for Plant Biology, Purdue University, West Lafayette, IN 47907, USA.
Science ; 385(6709): 671-678, 2024 08 09.
Article en En | MEDLINE | ID: mdl-39116217
ABSTRACT
Prymnesium parvum are harmful haptophyte algae that cause massive environmental fish kills. Their polyketide polyether toxins, the prymnesins, are among the largest nonpolymeric compounds in nature and have biosynthetic origins that have remained enigmatic for more than 40 years. In this work, we report the "PKZILLAs," massive P. parvum polyketide synthase (PKS) genes that have evaded previous detection. PKZILLA-1 and -2 encode giant protein products of 4.7 and 3.2 megadaltons that have 140 and 99 enzyme domains. Their predicted polyene product matches the proposed pre-prymnesin precursor of the 90-carbon-backbone A-type prymnesins. We further characterize the variant PKZILLA-B1, which is responsible for the shorter B-type analog prymnesin-B1, from P. parvum RCC3426 and thus establish a general model of haptophyte polyether biosynthetic logic. This work expands expectations of genetic and enzymatic size limits in biology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sintasas Poliquetidas / Haptophyta / Toxinas Poliéteres Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sintasas Poliquetidas / Haptophyta / Toxinas Poliéteres Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos