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Phylogenomics reveals subfamilies of fungal nonribosomal peptide synthetases and their evolutionary relationships.

Bushley KE, Turgeon BG - BMC Evol. Biol. (2010)

Bottom Line: We also characterized relationships of fungal NRPSs, a representative sampling of bacterial NRPSs, and related adenylating enzymes, including alpha-aminoadipate reductases (AARs) involved in lysine biosynthesis in fungi.It also demonstrates that the alpha-aminoadipate reductases involved in lysine biosynthesis in fungi are closely related to mono/bi-modular NRPSs.The euascomycete-only NRPS subfamily, in particular, shows evidence for extensive gain and loss of domains suggestive of the contribution of domain duplication and loss in responding to niche-specific pressures.

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Affiliation: Department of Plant Pathology & Plant-Microbe Biology, 334 Plant Science Bldg, Cornell University, Ithaca, NY, 14853, USA.

ABSTRACT

Background: Nonribosomal peptide synthetases (NRPSs) are multimodular enzymes, found in fungi and bacteria, which biosynthesize peptides without the aid of ribosomes. Although their metabolite products have been the subject of intense investigation due to their life-saving roles as medicinals and injurious roles as mycotoxins and virulence factors, little is known of the phylogenetic relationships of the corresponding NRPSs or whether they can be ranked into subgroups of common function. We identified genes (NPS) encoding NRPS and NRPS-like proteins in 38 fungal genomes and undertook phylogenomic analyses in order to identify fungal NRPS subfamilies, assess taxonomic distribution, evaluate levels of conservation across subfamilies, and address mechanisms of evolution of multimodular NRPSs. We also characterized relationships of fungal NRPSs, a representative sampling of bacterial NRPSs, and related adenylating enzymes, including alpha-aminoadipate reductases (AARs) involved in lysine biosynthesis in fungi.

Results: Phylogenomic analysis identified nine major subfamilies of fungal NRPSs which fell into two main groups: one corresponds to NPS genes encoding primarily mono/bi-modular enzymes which grouped with bacterial NRPSs and the other includes genes encoding primarily multimodular and exclusively fungal NRPSs. AARs shared a closer phylogenetic relationship to NRPSs than to other acyl-adenylating enzymes. Phylogenetic analyses and taxonomic distribution suggest that several mono/bi-modular subfamilies arose either prior to, or early in, the evolution of fungi, while two multimodular groups appear restricted to and expanded in fungi. The older mono/bi-modular subfamilies show conserved domain architectures suggestive of functional conservation, while multimodular NRPSs, particularly those unique to euascomycetes, show a diversity of architectures and of genetic mechanisms generating this diversity.

Conclusions: This work is the first to characterize subfamilies of fungal NRPSs. Our analyses suggest that mono/bi-modular NRPSs have more ancient origins and more conserved domain architectures than most multimodular NRPSs. It also demonstrates that the alpha-aminoadipate reductases involved in lysine biosynthesis in fungi are closely related to mono/bi-modular NRPSs. Several groups of mono/bi-modular NRPS metabolites are predicted to play more pivotal roles in cellular metabolism than products of multimodular NRPSs. In contrast, multimodular subfamilies of NRPSs are of more recent origin, are restricted to fungi, show less stable domain architectures, and biosynthesize metabolites which perform more niche-specific functions than mono/bi-modular NRPS products. The euascomycete-only NRPS subfamily, in particular, shows evidence for extensive gain and loss of domains suggestive of the contribution of domain duplication and loss in responding to niche-specific pressures.

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Number and range of NRPSs and A domains for each subfamily. A. Average and range (lowest to highest) number of NRPS-encoding genes in each subfamily per euascomycete genome shows that the EAS subfamily has both the highest average number of genes and the highest variation in copy number among species. PKS;NRPSs and ChNPS12 subfamilies also have substantial variation in numbers of NRPS-encoding genes among species. B. Average and range (lowest to highest) of the number of A domains/NRPS in euascomycete genomes for each subfamily shows that the EAS subfamily also has by far the greatest variation in number of A domains/NRPS followed by the CYCLO, and SID subfamilies.
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Figure 10: Number and range of NRPSs and A domains for each subfamily. A. Average and range (lowest to highest) number of NRPS-encoding genes in each subfamily per euascomycete genome shows that the EAS subfamily has both the highest average number of genes and the highest variation in copy number among species. PKS;NRPSs and ChNPS12 subfamilies also have substantial variation in numbers of NRPS-encoding genes among species. B. Average and range (lowest to highest) of the number of A domains/NRPS in euascomycete genomes for each subfamily shows that the EAS subfamily also has by far the greatest variation in number of A domains/NRPS followed by the CYCLO, and SID subfamilies.

Mentions: The range of variation in copy number of NRPS-encoding genes and in number of A domains/NRPS for each subfamily is shown for Euascomycete taxa only in Fig. 10. Variation in gene copy number is the highest for the EAS subfamily but both the PKS;NRPS and ChNPS12 subfamilies also show substantial variation (Fig. 10A). The EAS subfamily also shows by far the greatest variation in number of A domains/NRPS, followed by CYCLO and SID subfamilies, suggestive of less stable domain architectures and higher rates of intragenic domain duplication for these three groups. All of the remaining mono/bi-modular subfamilies show remarkably conserved domain architectures (Fig. 5, 10B), supporting available functional data which suggests these groups may have more central conserved roles in metabolism.


Phylogenomics reveals subfamilies of fungal nonribosomal peptide synthetases and their evolutionary relationships.

Bushley KE, Turgeon BG - BMC Evol. Biol. (2010)

Number and range of NRPSs and A domains for each subfamily. A. Average and range (lowest to highest) number of NRPS-encoding genes in each subfamily per euascomycete genome shows that the EAS subfamily has both the highest average number of genes and the highest variation in copy number among species. PKS;NRPSs and ChNPS12 subfamilies also have substantial variation in numbers of NRPS-encoding genes among species. B. Average and range (lowest to highest) of the number of A domains/NRPS in euascomycete genomes for each subfamily shows that the EAS subfamily also has by far the greatest variation in number of A domains/NRPS followed by the CYCLO, and SID subfamilies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2823734&req=5

Figure 10: Number and range of NRPSs and A domains for each subfamily. A. Average and range (lowest to highest) number of NRPS-encoding genes in each subfamily per euascomycete genome shows that the EAS subfamily has both the highest average number of genes and the highest variation in copy number among species. PKS;NRPSs and ChNPS12 subfamilies also have substantial variation in numbers of NRPS-encoding genes among species. B. Average and range (lowest to highest) of the number of A domains/NRPS in euascomycete genomes for each subfamily shows that the EAS subfamily also has by far the greatest variation in number of A domains/NRPS followed by the CYCLO, and SID subfamilies.
Mentions: The range of variation in copy number of NRPS-encoding genes and in number of A domains/NRPS for each subfamily is shown for Euascomycete taxa only in Fig. 10. Variation in gene copy number is the highest for the EAS subfamily but both the PKS;NRPS and ChNPS12 subfamilies also show substantial variation (Fig. 10A). The EAS subfamily also shows by far the greatest variation in number of A domains/NRPS, followed by CYCLO and SID subfamilies, suggestive of less stable domain architectures and higher rates of intragenic domain duplication for these three groups. All of the remaining mono/bi-modular subfamilies show remarkably conserved domain architectures (Fig. 5, 10B), supporting available functional data which suggests these groups may have more central conserved roles in metabolism.

Bottom Line: We also characterized relationships of fungal NRPSs, a representative sampling of bacterial NRPSs, and related adenylating enzymes, including alpha-aminoadipate reductases (AARs) involved in lysine biosynthesis in fungi.It also demonstrates that the alpha-aminoadipate reductases involved in lysine biosynthesis in fungi are closely related to mono/bi-modular NRPSs.The euascomycete-only NRPS subfamily, in particular, shows evidence for extensive gain and loss of domains suggestive of the contribution of domain duplication and loss in responding to niche-specific pressures.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Plant Pathology & Plant-Microbe Biology, 334 Plant Science Bldg, Cornell University, Ithaca, NY, 14853, USA.

ABSTRACT

Background: Nonribosomal peptide synthetases (NRPSs) are multimodular enzymes, found in fungi and bacteria, which biosynthesize peptides without the aid of ribosomes. Although their metabolite products have been the subject of intense investigation due to their life-saving roles as medicinals and injurious roles as mycotoxins and virulence factors, little is known of the phylogenetic relationships of the corresponding NRPSs or whether they can be ranked into subgroups of common function. We identified genes (NPS) encoding NRPS and NRPS-like proteins in 38 fungal genomes and undertook phylogenomic analyses in order to identify fungal NRPS subfamilies, assess taxonomic distribution, evaluate levels of conservation across subfamilies, and address mechanisms of evolution of multimodular NRPSs. We also characterized relationships of fungal NRPSs, a representative sampling of bacterial NRPSs, and related adenylating enzymes, including alpha-aminoadipate reductases (AARs) involved in lysine biosynthesis in fungi.

Results: Phylogenomic analysis identified nine major subfamilies of fungal NRPSs which fell into two main groups: one corresponds to NPS genes encoding primarily mono/bi-modular enzymes which grouped with bacterial NRPSs and the other includes genes encoding primarily multimodular and exclusively fungal NRPSs. AARs shared a closer phylogenetic relationship to NRPSs than to other acyl-adenylating enzymes. Phylogenetic analyses and taxonomic distribution suggest that several mono/bi-modular subfamilies arose either prior to, or early in, the evolution of fungi, while two multimodular groups appear restricted to and expanded in fungi. The older mono/bi-modular subfamilies show conserved domain architectures suggestive of functional conservation, while multimodular NRPSs, particularly those unique to euascomycetes, show a diversity of architectures and of genetic mechanisms generating this diversity.

Conclusions: This work is the first to characterize subfamilies of fungal NRPSs. Our analyses suggest that mono/bi-modular NRPSs have more ancient origins and more conserved domain architectures than most multimodular NRPSs. It also demonstrates that the alpha-aminoadipate reductases involved in lysine biosynthesis in fungi are closely related to mono/bi-modular NRPSs. Several groups of mono/bi-modular NRPS metabolites are predicted to play more pivotal roles in cellular metabolism than products of multimodular NRPSs. In contrast, multimodular subfamilies of NRPSs are of more recent origin, are restricted to fungi, show less stable domain architectures, and biosynthesize metabolites which perform more niche-specific functions than mono/bi-modular NRPS products. The euascomycete-only NRPS subfamily, in particular, shows evidence for extensive gain and loss of domains suggestive of the contribution of domain duplication and loss in responding to niche-specific pressures.

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