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J Am Chem Soc
2022 Jun 01;14421:9363-9371. doi: 10.1021/jacs.2c01416.
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Sea Urchin Polyketide Synthase SpPks1 Produces the Naphthalene Precursor to Echinoderm Pigments.
Li F
,
Lin Z
,
Torres JP
,
Hill EA
,
Li D
,
Townsend CA
,
Schmidt EW
.
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Nearly every animal species on Earth contains a unique polyketide synthase (PKS) encoded in its genome, yet no animal-clade PKS has been biochemically characterized, and even the chemical products of these ubiquitous enzymes are known in only a few cases. The earliest animal genome-encoded PKS gene to be identified was SpPks1 from sea urchins. Previous genetic knockdown experiments implicated SpPks1 in synthesis of the sea urchin pigment echinochrome. Here, we express and purify SpPks1, performing biochemical experiments to demonstrate that the sea urchin protein is responsible for the synthesis of 2-acetyl-1,3,6,8-tetrahydroxynaphthalene (ATHN). Since ATHN is a plausible precursor of echinochromes, this result defines a biosynthetic pathway to the ubiquitous echinoderm pigments and rewrites the previous hypothesis for echinochrome biosynthesis. Truncation experiments showed that, unlike other type I iterative PKSs so far characterized, SpPks1 produces the naphthalene core using solely ketoacylsynthase (KS), acyltransferase, and acyl carrier protein domains, delineating a unique class of animal nonreducing aromatic PKSs (aPKSs). A series of amino acids in the KS domain define the family and are likely crucial in cyclization activity. Phylogenetic analyses indicate that SpPks1 and its homologs are widespread in echinoderms and their closest relatives, the acorn worms, reinforcing their fundamental importance to echinoderm biology. While the animal microbiome is known to produce aromatic polyketides, this work provides biochemical evidence that animals themselves also harbor ancient, convergent, dedicated pathways to carbocyclic aromatic polyketides. More fundamentally, biochemical analysis of SpPks1 begins to define the vast and unexplored biosynthetic space of the ubiquitous animal PKS family.
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35588530
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Alberts,
Discovery, biochemistry and biology of lovastatin.
1988, Pubmed
Alberts,
Discovery, biochemistry and biology of lovastatin.
1988,
Pubmed
Beeble,
Expression pattern of polyketide synthase-2 during sea urchin development.
2012,
Pubmed
,
Echinobase
Bond,
Saccharomyces cerevisiae as a tool for mining, studying and engineering fungal polyketide synthases.
2016,
Pubmed
Calestani,
These Colors Don't Run: Regulation of Pigment-Biosynthesis in Echinoderms.
2018,
Pubmed
,
Echinobase
Calestani,
Isolation of pigment cell specific genes in the sea urchin embryo by differential macroarray screening.
2003,
Pubmed
,
Echinobase
Castoe,
A novel group of type I polyketide synthases (PKS) in animals and the complex phylogenomics of PKSs.
2007,
Pubmed
,
Echinobase
Chen,
Extender unit and acyl carrier protein specificity of ketosynthase domains of the 6-deoxyerythronolide B synthase.
2006,
Pubmed
Cooke,
Genetic Mapping and Biochemical Basis of Yellow Feather Pigmentation in Budgerigars.
2017,
Pubmed
Crawford,
Deconstruction of iterative multidomain polyketide synthase function.
2008,
Pubmed
Dreier,
Mechanistic analysis of a type II polyketide synthase. Role of conserved residues in the beta-ketoacyl synthase-chain length factor heterodimer.
2000,
Pubmed
Du,
The trRosetta server for fast and accurate protein structure prediction.
2021,
Pubmed
Fujii,
Identification of Claisen cyclase domain in fungal polyketide synthase WA, a naphthopyrone synthase of Aspergillus nidulans.
2001,
Pubmed
Gao,
Formation of an Angular Aromatic Polyketide from a Linear Anthrene Precursor via Oxidative Rearrangement.
2017,
Pubmed
Hertweck,
The biosynthetic logic of polyketide diversity.
2009,
Pubmed
Hojo,
Unexpected link between polyketide synthase and calcium carbonate biomineralization.
2015,
Pubmed
,
Echinobase
Hou,
Naphthoquinones of the spinochrome class: occurrence, isolation, biosynthesis and biomedical applications.
2018,
Pubmed
,
Echinobase
Izumikawa,
Expression and characterization of the type III polyketide synthase 1,3,6,8-tetrahydroxynaphthalene synthase from Streptomyces coelicolor A3(2).
2003,
Pubmed
Keatinge-Clay,
An antibiotic factory caught in action.
2004,
Pubmed
Kinjo,
HpBase: A genome database of a sea urchin, Hemicentrotus pulcherrimus.
2018,
Pubmed
,
Echinobase
Lebed'ko,
Effect of Antioxidant Echinochrome A on Bleomycin-Induced Pulmonary Fibrosis.
2015,
Pubmed
Lee,
Determination of the extent of phosphopantetheinylation of polyketide synthases expressed in Escherichia coli and Saccharomyces cerevisiae.
2009,
Pubmed
Little,
Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis.
2022,
Pubmed
Liu,
The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases.
2005,
Pubmed
Liu,
Establishment of knockout adult sea urchins by using a CRISPR-Cas9 system.
2019,
Pubmed
,
Echinobase
Ma,
Complete reconstitution of a highly reducing iterative polyketide synthase.
2009,
Pubmed
McDaniel,
Engineered biosynthesis of novel polyketides: influence of a downstream enzyme on the catalytic specificity of a minimal aromatic polyketide synthase.
1994,
Pubmed
Mohamed,
Echinochrome Exhibits Antitumor Activity against Ehrlich Ascites Carcinoma in Swiss Albino Mice.
2021,
Pubmed
,
Echinobase
Newman,
Systematic domain swaps of iterative, nonreducing polyketide synthases provide a mechanistic understanding and rationale for catalytic reprogramming.
2014,
Pubmed
O'Brien,
Computational identification and analysis of orphan assembly-line polyketide synthases.
2014,
Pubmed
Pfeifer,
Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli.
2001,
Pubmed
Pozharitskaya,
Antiallergic effects of pigments isolated from green sea urchin (Strongylocentrotus droebachiensis) shells.
2013,
Pubmed
,
Echinobase
Reid,
A model of structure and catalysis for ketoreductase domains in modular polyketide synthases.
2003,
Pubmed
Salaque,
[On the biosynthesis of echinochrome A by the sea urchin Arbacia pustulosa].
1967,
Pubmed
,
Echinobase
Shou,
A hybrid polyketide-nonribosomal peptide in nematodes that promotes larval survival.
2016,
Pubmed
Singh,
The distribution of quinone pigments in echinoderms.
1967,
Pubmed
,
Echinobase
Staunton,
Biosynthesis of Erythromycin and Rapamycin.
1997,
Pubmed
Torres,
Animal biosynthesis of complex polyketides in a photosynthetic partnership.
2020,
Pubmed
Tsai,
Pentaketide melanin biosynthesis in Aspergillus fumigatus requires chain-length shortening of a heptaketide precursor.
2001,
Pubmed
Vagstad,
Characterization of a fungal thioesterase having Claisen cyclase and deacetylase activities in melanin biosynthesis.
2012,
Pubmed
Vagstad,
Combinatorial domain swaps provide insights into the rules of fungal polyketide synthase programming and the rational synthesis of non-native aromatic products.
2013,
Pubmed
Waldman,
Lomaiviticin biosynthesis employs a new strategy for starter unit generation.
2014,
Pubmed
Wang,
Structural basis for the biosynthesis of lovastatin.
2021,
Pubmed
Wessel,
Genetic manipulation of the pigment pathway in a sea urchin reveals distinct lineage commitment prior to metamorphosis in the bilateral to radial body plan transition.
2020,
Pubmed
,
Echinobase
Wheeler,
New biosynthetic step in the melanin pathway of Wangiella (Exophiala) dermatitidis: evidence for 2-acetyl-1,3,6,8-Tetrahydroxynaphthalene as a novel precursor.
2008,
Pubmed
Wolkenstein,
Persistent and widespread occurrence of bioactive quinone pigments during post-Paleozoic crinoid diversification.
2015,
Pubmed
,
Echinobase
Xie,
Epimerase and Reductase Activities of Polyketide Synthase Ketoreductase Domains Utilize the Same Conserved Tyrosine and Serine Residues.
2016,
Pubmed
Yaguchi,
Establishment of homozygous knock-out sea urchins.
2020,
Pubmed
,
Echinobase
Zhang,
Engineered biosynthesis of bacterial aromatic polyketides in Escherichia coli.
2008,
Pubmed
Zhao,
Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis.
2008,
Pubmed
