Biochemistry of Polyketide Synthases

Gokhale, Rajesh S.; Tuteja, Dipika

doi:10.1002/9783527620937.ch12

Cited by 8 publications

(3 citation statements)

References 129 publications

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“…In this study, PKS genes were identified by screening the PKS sequence database, especially the domain database, which include: ketoacyl synthase (KS), acyl transferase (AT), ketoreductase (KR), dehydratase (DH), enoyl reductase (ER), and acyl carrier protein (ACP, also known as PP domain). The KS, AT, and ACP domains are essential for PKS genes [ 66 ]. Two PKS genes were identified to have multiple domains above: KS-AT-KR-ACP in CDC_141, and KS-AT-DH-ER-KR-ACP in CDC_165.…”

Section: Discussionmentioning

confidence: 99%

Genomic characterization of the conditionally dispensable chromosome in Alternaria arborescens provides evidence for horizontal gene transfer

Chen

Peever

et al. 2012

BMC Genomics

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BackgroundFungal plant pathogens cause serious agricultural losses worldwide. Alternaria arborescens is a major pathogen of tomato, with its virulence determined by the presence of a conditionally dispensable chromosome (CDC) carrying host-specific toxin genes. Genes encoding these toxins are well-studied, however the genomic content and organization of the CDC is not known.ResultsTo gain a richer understanding of the molecular determinants of virulence and the evolution of pathogenicity, we performed whole genome sequencing of A. arborescens. Here we present the de-novo assembly of the CDC and its predicted gene content. Also presented is hybridization data validating the CDC assembly. Predicted genes were functionally annotated through BLAST. Gene ontology terms were assigned, and conserved domains were identified. Differences in nucleotide usage were found between CDC genes and those on the essential chromosome (EC), including GC3-content, codon usage bias, and repeat region load. Genes carrying PKS and NRPS domains were identified in clusters on the CDC and evidence supporting the origin of the CDC through horizontal transfer from an unrelated fungus was found.ConclusionsWe provide evidence supporting the hypothesis that the CDC in A. arborescens was acquired through horizontal transfer, likely from an unrelated fungus. We also identified several predicted CDC genes under positive selection that may serve as candidate virulence factors.

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Section: Discussionmentioning

confidence: 99%

Genomic characterization of the conditionally dispensable chromosome in Alternaria arborescens provides evidence for horizontal gene transfer

Chen

Peever

et al. 2012

BMC Genomics

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“…PKS enzymes are multi-functional complexes consisting of a minimal set of catalytic domains, namely ketoacylsynthase (KS), acyl transferase (AT) and acyl carrier protein (ACP), which are required for function. Three further domains (ketoacylreductases (KR), dehydrases (DH) and enolreductases (ER)) can be optionally present, and when present, these are responsible for the broad variety of polyketide structures found in dinoflagellates [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic characterisation and genomic glimps into the toxigenic dinoflagellate Azadinium spinosum, with emphasis on polykeitde synthase genes

et al. 2015

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BackgroundUnicellular dinoflagellates are an important group of primary producers within the marine plankton community. Many of these species are capable of forming harmful algae blooms (HABs) and of producing potent phycotoxins, thereby causing deleterious impacts on their environment and posing a threat to human health. The recently discovered toxigenic dinoflagellate Azadinium spinosum is known to produce azaspiracid toxins. These toxins are most likely produced by polyketide synthases (PKS). Recently, PKS I-like transcripts have been identified in a number of dinoflagellate species. Despite the global distribution of A. spinosum, little is known about molecular features. In this study, we investigate the genomic and transcriptomic features of A. spinosum with a focus on polyketide synthesis and PKS evolution.ResultsWe identify orphan and homologous genes by comparing the transcriptome data of A. spinosum with a diverse set of 18 other dinoflagellates, five further species out of the Rhizaria Alveolate Stramelopile (RAS)-group, and one representative from the Plantae. The number of orphan genes in the analysed dinoflagellate species averaged 27%. In contrast, within the A. spinosum transcriptome, we discovered 12,661 orphan transcripts (18%). The dinoflagellates toxins known as azaspiracids (AZAs) are structurally polyethers; we therefore analyse the transcriptome of A. spinosum with respect to polyketide synthases (PKSs), the primary biosynthetic enzymes in polyketide synthesis. We find all the genes thought to be potentially essential for polyketide toxin synthesis to be expressed in A. spinosum, whose PKS transcripts fall into the dinoflagellate sub-clade in PKS evolution.ConclusionsOverall, we demonstrate that the number of orphan genes in the A. spinosum genome is relatively small compared to other dinoflagellate species. In addition, all PKS domains needed to produce the azaspiracid carbon backbone are present in A. spinosum. Our study underscores the extraordinary evolution of such gene clusters and, in particular, supports the proposed structural and functional paradigm for PKS Type I genes in dinoflagellates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-014-1205-6) contains supplementary material, which is available to authorized users.

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“…Additional domains participate in the modification of the carbonyl group; these include ketoreductase (KR), dehydratase (DH) and enoyl reductase (ER) domains. A thioesterase (TE) domain catalyzes the release of the polyketide product from the last PKS participating in chain elongation [9][10][11].…”

Section: Inroductionmentioning

confidence: 99%

Computational Prediction of Properties and Analysis of Molecular Phylogenetics of Polyketide Synthases in Three Species of Actinomycetes

Moosawi¹,

Mohabatkar²,

Mohsenzadeh

2010

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Polyketides are secondary metabolites of microorganisms synthesized by serialized reactions of a set of enzymes called polyketide synthases (PKS). As many infectious microorganisms are acquiring tolerance to antibiotics, the need for novel medicines is increasing. Recently, various methods are being used for drug discovery, including gene manipulation for biosynthesis of antibiotics such as polyketides. Due to their importance as drugs, the volume of data on polyketides is rapidly increasing. In the present paper, by using SEARCHPKS and ASMPKS servers, domain identification, and domain organization, substrate specificity of AT domain, domain assembly and chemical moiety of three Actinomycetes i.e., Mycobacterium abscessus, Micromonospora chalcea and Streptomyces achromogenes are analyzed. So far, no secondary metabolite of any of these bacteria is known. Here, it was demonstrated that KR1, KR2 and KR3 domains from M. chalcea, KR5 domain from M. abscessus and KR6 domain from S. achromogenes could be assigned as B1-type, while KR4 domain from M. abscessus and KR7 domain from S. achromogenes could be assigned as A1 type. Substrate specificity of AT1 and AT2 of M. abscessus predicted to be malonate. AT2 domain of PKS protein from S. achromogenes also selected as malonate. Methylmalonate substrate was predicted for AT1 and AT3 domains. All of the AT domains in modules of PKS protein of M. chalcea were predicted to be specific for methylmalonate. Analysis of folding rate of these proteins showed that the logarithm of (kf) decreased in proportion to protein chain length. We have also performed a comprehensive phylogenetics analysis of AT and DH domains with FabA, FabZ and dehydratase proteins of various bacteria and secondary metabolites. The phylogenetic tree derived from these sequences reflects the long joint evolution process.

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Biochemistry of Polyketide Synthases

Cited by 8 publications

References 129 publications

Genomic characterization of the conditionally dispensable chromosome in Alternaria arborescens provides evidence for horizontal gene transfer

Genomic characterization of the conditionally dispensable chromosome in Alternaria arborescens provides evidence for horizontal gene transfer

Transcriptomic characterisation and genomic glimps into the toxigenic dinoflagellate Azadinium spinosum, with emphasis on polykeitde synthase genes

Computational Prediction of Properties and Analysis of Molecular Phylogenetics of Polyketide Synthases in Three Species of Actinomycetes

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