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Classification and substrate head-group specificity of membrane fatty acid desaturases

View Article: PubMed Central - PubMed

ABSTRACT

Membrane fatty acid desaturases are a diverse superfamily of enzymes that catalyze the introduction of double bonds into fatty acids. They are essential in a range of metabolic processes, such as the production of omega-3 fatty acids. However, our structure–function understanding of this superfamily is still developing and their range of activities and substrate specificities are broad, and often overlapping, which has made their systematic characterization challenging. A central issue with characterizing these proteins has been the lack of a structural model, which has been overcome with the recent publication of the crystal structures of two mammalian fatty acid desaturases. In this work, we have used sequence similarity networks to investigate the similarity among over 5000 related membrane fatty acid desaturase sequences, leading to a detailed classification of the superfamily, families and subfamilies with regard to their function and substrate head-group specificity. This work will facilitate rapid prediction of the function and specificity of new and existing sequences, as well as forming a basis for future efforts to manipulate the substrate specificity of these proteins for biotechnology applications.

No MeSH data available.


The representative sub-clusters within the FE1 cluster. A and B are the same networks generated from the FE1 cluster in Fig. 2 at a higher stringency, LogE < − 65. The nodes are coloured by organism kingdom information (A) and their substrate specificities reported in the literature (B).
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f0040: The representative sub-clusters within the FE1 cluster. A and B are the same networks generated from the FE1 cluster in Fig. 2 at a higher stringency, LogE < − 65. The nodes are coloured by organism kingdom information (A) and their substrate specificities reported in the literature (B).

Mentions: Increasing the LogE filter to <− 65 can further differentiate the FE1 cluster, revealing the presence of clusters with distinct lipid head-group preferences including a sphingolipids/acyl-PC-specific cluster (FE1-S), a predominantly acyl-PC-specific cluster (FE1-PC) and acyl-CoA-specific proteins (FE1-AC) (Fig. 8). The separation of sequences within the FE1 sub-cluster is supported by a phylogenetic analysis of the functionally characterized FE desaturases (Fig. 9). The FE1-AC sub-cluster includes the animal Δ5 and Δ6 acyl-CoA desaturases, as well as the algal and fungal acyl-CoA desaturases. The FE1-PC sub-cluster includes genes from C. elegans, moss and liverworts. Within this sub-cluster, Marchantia polymorpha Δ6 desaturase (UniProt ID: Q696V8) has been shown to have some promiscuous activity with acyl-CoA substrates in addition to acyl-PC substrates [61]. The FE1-S sub-cluster is complex and difficult to resolve at a LogE < − 65 filter, and includes both acyl-PC and acyl-SP desaturases. Within the FE1-S sub-cluster, higher plant FE desaturases cluster with a group of fungal proteins.


Classification and substrate head-group specificity of membrane fatty acid desaturases
The representative sub-clusters within the FE1 cluster. A and B are the same networks generated from the FE1 cluster in Fig. 2 at a higher stringency, LogE < − 65. The nodes are coloured by organism kingdom information (A) and their substrate specificities reported in the literature (B).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037126&req=5

f0040: The representative sub-clusters within the FE1 cluster. A and B are the same networks generated from the FE1 cluster in Fig. 2 at a higher stringency, LogE < − 65. The nodes are coloured by organism kingdom information (A) and their substrate specificities reported in the literature (B).
Mentions: Increasing the LogE filter to <− 65 can further differentiate the FE1 cluster, revealing the presence of clusters with distinct lipid head-group preferences including a sphingolipids/acyl-PC-specific cluster (FE1-S), a predominantly acyl-PC-specific cluster (FE1-PC) and acyl-CoA-specific proteins (FE1-AC) (Fig. 8). The separation of sequences within the FE1 sub-cluster is supported by a phylogenetic analysis of the functionally characterized FE desaturases (Fig. 9). The FE1-AC sub-cluster includes the animal Δ5 and Δ6 acyl-CoA desaturases, as well as the algal and fungal acyl-CoA desaturases. The FE1-PC sub-cluster includes genes from C. elegans, moss and liverworts. Within this sub-cluster, Marchantia polymorpha Δ6 desaturase (UniProt ID: Q696V8) has been shown to have some promiscuous activity with acyl-CoA substrates in addition to acyl-PC substrates [61]. The FE1-S sub-cluster is complex and difficult to resolve at a LogE < − 65 filter, and includes both acyl-PC and acyl-SP desaturases. Within the FE1-S sub-cluster, higher plant FE desaturases cluster with a group of fungal proteins.

View Article: PubMed Central - PubMed

ABSTRACT

Membrane fatty acid desaturases are a diverse superfamily of enzymes that catalyze the introduction of double bonds into fatty acids. They are essential in a range of metabolic processes, such as the production of omega-3 fatty acids. However, our structure&ndash;function understanding of this superfamily is still developing and their range of activities and substrate specificities are broad, and often overlapping, which has made their systematic characterization challenging. A central issue with characterizing these proteins has been the lack of a structural model, which has been overcome with the recent publication of the crystal structures of two mammalian fatty acid desaturases. In this work, we have used sequence similarity networks to investigate the similarity among over 5000 related membrane fatty acid desaturase sequences, leading to a detailed classification of the superfamily, families and subfamilies with regard to their function and substrate head-group specificity. This work will facilitate rapid prediction of the function and specificity of new and existing sequences, as well as forming a basis for future efforts to manipulate the substrate specificity of these proteins for biotechnology applications.

No MeSH data available.