Giant polyketide synthase enzymes in the biosynthesis of giant marine polyether toxins.

Autor: 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.; Purdue Center for Plant Biology, Purdue University, West Lafayette, IN 47907, USA., Watervoort NF; Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.; Purdue Center for Plant Biology, Purdue University, West Lafayette, IN 47907, USA., Auber RP; Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.; Purdue Center for Plant Biology, Purdue University, West Lafayette, IN 47907, USA., Gonzalez DJ; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA., Wisecaver JH; Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.; Purdue Center for Plant Biology, Purdue University, West Lafayette, IN 47907, USA., Moore BS; Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and University of California, San Diego, La Jolla, CA 92093, USA.; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Aug 09; Vol. 385 (6709), pp. 671-678. Date of Electronic Publication: 2024 Aug 08.
DOI: 10.1126/science.ado3290
Abstrakt: 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.
Databáze: MEDLINE
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