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Evolution of Chemical Diversity in a Group of Non-Reduced Polyketide Gene Clusters: Using Phylogenetics to Inform the Search for Novel Fungal Natural Products.

Throckmorton K, Wiemann P, Keller NP - Toxins (Basel) (2015)

Bottom Line: Here, we focus on a group of non-reducing polyketide synthases (NR-PKSs) in the fungal phylum Ascomycota that lack a thioesterase domain for product release, group V.We discuss the modification of and transitions between these chemical classes, the requisite enzymes, and the evolution of the SM gene clusters that encode them.Integrating this information, we predict the likely products of related but uncharacterized SM clusters, and we speculate upon the utility of these classes of SMs as virulence factors or chemical defenses to various plant, animal, and insect pathogens, as well as mutualistic fungi.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University of Wisconsin-Madison, 425 Henry Mall, Madison, WI 53706-1580, USA. kthrockmorto@wisc.edu.

ABSTRACT
Fungal polyketides are a diverse class of natural products, or secondary metabolites (SMs), with a wide range of bioactivities often associated with toxicity. Here, we focus on a group of non-reducing polyketide synthases (NR-PKSs) in the fungal phylum Ascomycota that lack a thioesterase domain for product release, group V. Although widespread in ascomycete taxa, this group of NR-PKSs is notably absent in the mycotoxigenic genus Fusarium and, surprisingly, found in genera not known for their secondary metabolite production (e.g., the mycorrhizal genus Oidiodendron, the powdery mildew genus Blumeria, and the causative agent of white-nose syndrome in bats, Pseudogymnoascus destructans). This group of NR-PKSs, in association with the other enzymes encoded by their gene clusters, produces a variety of different chemical classes including naphthacenediones, anthraquinones, benzophenones, grisandienes, and diphenyl ethers. We discuss the modification of and transitions between these chemical classes, the requisite enzymes, and the evolution of the SM gene clusters that encode them. Integrating this information, we predict the likely products of related but uncharacterized SM clusters, and we speculate upon the utility of these classes of SMs as virulence factors or chemical defenses to various plant, animal, and insect pathogens, as well as mutualistic fungi.

No MeSH data available.


Related in: MedlinePlus

A diagram showing the domains of typical highly reducing (HR), non-reducing (NR), and group V NR type I fungal polyketide synthases. SAT = starter-unit:ACP transacylase, KS = β-ketoacyl synthase, MAT = malonyl-CoA:ACP transacylase, DH = dehydratase, CMeT = C-methyltransferase, ER = enoyl reductase, KR = ketoreductase, PT = product template, ACP = acyl carrier protein, TE = thioesterase, CYC = Claisen cyclase.
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toxins-07-03572-f001: A diagram showing the domains of typical highly reducing (HR), non-reducing (NR), and group V NR type I fungal polyketide synthases. SAT = starter-unit:ACP transacylase, KS = β-ketoacyl synthase, MAT = malonyl-CoA:ACP transacylase, DH = dehydratase, CMeT = C-methyltransferase, ER = enoyl reductase, KR = ketoreductase, PT = product template, ACP = acyl carrier protein, TE = thioesterase, CYC = Claisen cyclase.

Mentions: Most fungal PKSs are multi-functional enzymes known as iterative type I PKSs, where each catalytic domain is encoded in one gene, though a few fungal PKSs are of type III [32]. There are two main classes of type I PKS known as non-reducing (NR) and highly reducing (HR). All PKSs harbor three essential domains—the β-ketoacyl synthase (KS), malonyl-CoA:acyl carrier protein transacylase (MAT), and acyl carrier protein (ACP) domains—however, NR- and HR-PKSs vary in their catalytic domains that impact the reduction or dehydration steps of the growing carbon chain (Figure 1). The minimal architecture of HR-PKSs is typically composed of ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) domains, thereby resembling fatty acid synthases (FASs). Another key difference is the presence of a C-methyltransferase (CMeT) domain found in most HR-PKSs and only in one subset of NR-PKSs (e.g., A. nidulans AfoE, [33]). However, despite the presence of CMeT domains in HR-PKSs, analysis in Fusarium spp. suggests that the domain can be non-functional [34].


Evolution of Chemical Diversity in a Group of Non-Reduced Polyketide Gene Clusters: Using Phylogenetics to Inform the Search for Novel Fungal Natural Products.

Throckmorton K, Wiemann P, Keller NP - Toxins (Basel) (2015)

A diagram showing the domains of typical highly reducing (HR), non-reducing (NR), and group V NR type I fungal polyketide synthases. SAT = starter-unit:ACP transacylase, KS = β-ketoacyl synthase, MAT = malonyl-CoA:ACP transacylase, DH = dehydratase, CMeT = C-methyltransferase, ER = enoyl reductase, KR = ketoreductase, PT = product template, ACP = acyl carrier protein, TE = thioesterase, CYC = Claisen cyclase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591646&req=5

toxins-07-03572-f001: A diagram showing the domains of typical highly reducing (HR), non-reducing (NR), and group V NR type I fungal polyketide synthases. SAT = starter-unit:ACP transacylase, KS = β-ketoacyl synthase, MAT = malonyl-CoA:ACP transacylase, DH = dehydratase, CMeT = C-methyltransferase, ER = enoyl reductase, KR = ketoreductase, PT = product template, ACP = acyl carrier protein, TE = thioesterase, CYC = Claisen cyclase.
Mentions: Most fungal PKSs are multi-functional enzymes known as iterative type I PKSs, where each catalytic domain is encoded in one gene, though a few fungal PKSs are of type III [32]. There are two main classes of type I PKS known as non-reducing (NR) and highly reducing (HR). All PKSs harbor three essential domains—the β-ketoacyl synthase (KS), malonyl-CoA:acyl carrier protein transacylase (MAT), and acyl carrier protein (ACP) domains—however, NR- and HR-PKSs vary in their catalytic domains that impact the reduction or dehydration steps of the growing carbon chain (Figure 1). The minimal architecture of HR-PKSs is typically composed of ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) domains, thereby resembling fatty acid synthases (FASs). Another key difference is the presence of a C-methyltransferase (CMeT) domain found in most HR-PKSs and only in one subset of NR-PKSs (e.g., A. nidulans AfoE, [33]). However, despite the presence of CMeT domains in HR-PKSs, analysis in Fusarium spp. suggests that the domain can be non-functional [34].

Bottom Line: Here, we focus on a group of non-reducing polyketide synthases (NR-PKSs) in the fungal phylum Ascomycota that lack a thioesterase domain for product release, group V.We discuss the modification of and transitions between these chemical classes, the requisite enzymes, and the evolution of the SM gene clusters that encode them.Integrating this information, we predict the likely products of related but uncharacterized SM clusters, and we speculate upon the utility of these classes of SMs as virulence factors or chemical defenses to various plant, animal, and insect pathogens, as well as mutualistic fungi.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University of Wisconsin-Madison, 425 Henry Mall, Madison, WI 53706-1580, USA. kthrockmorto@wisc.edu.

ABSTRACT
Fungal polyketides are a diverse class of natural products, or secondary metabolites (SMs), with a wide range of bioactivities often associated with toxicity. Here, we focus on a group of non-reducing polyketide synthases (NR-PKSs) in the fungal phylum Ascomycota that lack a thioesterase domain for product release, group V. Although widespread in ascomycete taxa, this group of NR-PKSs is notably absent in the mycotoxigenic genus Fusarium and, surprisingly, found in genera not known for their secondary metabolite production (e.g., the mycorrhizal genus Oidiodendron, the powdery mildew genus Blumeria, and the causative agent of white-nose syndrome in bats, Pseudogymnoascus destructans). This group of NR-PKSs, in association with the other enzymes encoded by their gene clusters, produces a variety of different chemical classes including naphthacenediones, anthraquinones, benzophenones, grisandienes, and diphenyl ethers. We discuss the modification of and transitions between these chemical classes, the requisite enzymes, and the evolution of the SM gene clusters that encode them. Integrating this information, we predict the likely products of related but uncharacterized SM clusters, and we speculate upon the utility of these classes of SMs as virulence factors or chemical defenses to various plant, animal, and insect pathogens, as well as mutualistic fungi.

No MeSH data available.


Related in: MedlinePlus