Abstract
BackgroundFilamentous fungi produce a vast amount of bioactive secondary metabolites (SMs) synthesized by e.g. hybrid polyketide synthase-nonribosomal peptide synthetase enzymes (PKS-NRPS; NRPS-PKS). While their domain structure suggests a common ancestor with other SM proteins, their evolutionary origin and dynamics in fungi are still unclear. Recent rational engineering approaches highlighted the possibility to reassemble hybrids into chimeras — suggesting molecular recombination as diversifying mechanism.ResultsPhylogenetic analysis of hybrids in 37 species – spanning 9 sections of Aspergillus and Penicillium chrysogenum – let us describe their dynamics throughout the genus Aspergillus. The tree topology indicates that three groups of PKS-NRPS as well as one group of NRPS-PKS hybrids developed independently from each other. Comparison to other SM genes lead to the conclusion that hybrids in Aspergilli have several PKS ancestors; in contrast, hybrids are monophyletic when compared to available NRPS genes — with the exception of a small group of NRPSs. Our analysis also revealed that certain NRPS-likes are derived from NRPSs, suggesting that the NRPS/NRPS-like relationship is dynamic and proteins can diverge from one function to another. An extended phylogenetic analysis including bacterial and fungal taxa revealed multiple ancestors of hybrids. Homologous hybrids are present in all sections which suggests frequent horizontal gene transfer between genera and a finite number of hybrids in fungi.ConclusionPhylogenetic distances between hybrids provide us with evidence for their evolution: Large inter-group distances indicate multiple independent events leading to the generation of hybrids, while short intra-group distances of hybrids from different taxonomic sections indicate frequent horizontal gene transfer. Our results are further supported by adding bacterial and fungal genera. Presence of related hybrid genes in all Ascomycetes suggests a frequent horizontal gene transfer between genera and a finite diversity of hybrids — also explaining their scarcity. The provided insights into relations of hybrids and other SM genes will serve in rational design of new hybrid enzymes.
Highlights
Filamentous fungi produce a vast amount of bioactive secondary metabolites (SMs) synthesized by e.g. hybrid polyketide synthase-nonribosomal peptide synthetase enzymes (PKS-non-ribosomal peptide synthetases (NRPSs); NRPS-polyketide synthases (PKSs))
Using genome data from 38 strains of the SMrich Aspergillus genus and Penicillium chrysogenum we describe the phylogenetic dynamics of PKS-NRPS and NRPS-PKS hybrids and relate them to PKSs and the structurally similar PKS-likes, as well as NRPSs and the structurally similar NRPS-likes
We are describing the diversity of rare PKS-NRPS and NRPS-PKS hybrids and compare them to related classes like PKSs and NRPSs
Summary
Filamentous fungi produce a vast amount of bioactive secondary metabolites (SMs) synthesized by e.g. hybrid polyketide synthase-nonribosomal peptide synthetase enzymes (PKS-NRPS; NRPS-PKS). While their domain structure suggests a common ancestor with other SM proteins, their evolutionary origin and dynamics in fungi are still unclear. Homologous hybrids are present in all sections which suggests frequent horizontal gene transfer between genera and a finite number of hybrids in fungi. Conclusion: Phylogenetic distances between hybrids provide us with evidence for their evolution: Large inter-group distances indicate multiple independent events leading to the generation of hybrids, while short intra-group distances of hybrids from different taxonomic sections indicate frequent horizontal gene transfer. For NRPSs, studies suggest duplication and loss of NRPSs, horizontal gene transfer (HGT) from bacteria to fungi, and gain and loss of domains as driver for diversity [10, 11]
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