Giant polyketide synthase enzymes in the biosynthesis of giant marine polyether toxins
Open accessPublished version of a preprint
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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Fast and accurate protein structure search with Foldseek
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Fast and accurate protein structure search with Foldseek
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- Authors
- Fallon, T. R., Shende, V. V., Wierzbicki, I. H., Pendleton, A. L., Watervoot, N. F., Auber, R. P., Gonzalez, D. J., Wisecaver, J. H., & Moore, B. S.
- Affiliations
- Scripps Institution of Oceanography (US)
- University of California San Diego (US)
- Purdue University West Lafayette (US)
- Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
- Corresponding author
- Fallon, Timothy R.
- Shende, Vikram V.
- Moore, Bradley S.
- ORCID
- Venue
- Science
- Published
- 2024-08-09
- Volume
- 385
- Issue
- 6709
- Pages
- 671-678
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC11416037
- OpenAlex
- W4401416795
- Cited by
- 39
- References
- 5
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 8
- FWCI
- 11.08
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- National Science Foundation (1831493)
- National Institutes of Health (1s10od026929-01)
- University of California, San Diego (#S10 OD026929)
- National Institute of General Medical Sciences (F32GM145146, R01GM085770)
- National Institute of Environmental Health Sciences (F32ES032276)
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Physical Sciences › Environmental Science › Environmental Chemistry › Marine Toxins and Detection Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Keywords
- polyketide synthase, prymnesins, Prymnesium parvum, polyether toxins, haptophyte algae, marine toxins, toxin production, fish kills
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