Project description:BackgroundCytochrome P450 proteins (CYPs) play diverse and pivotal roles in fungal metabolism and adaptation to specific ecological niches. Fungal genomes encode extremely variable "CYPomes" ranging from one to more than 300 CYPs. Despite the rapid growth of sequenced fungal and oomycete genomes and the resulting influx of predicted CYPs, the vast majority of CYPs remain functionally uncharacterized. To facilitate the curation and functional and evolutionary studies of CYPs, we previously developed Fungal Cytochrome P450 Database (FCPD), which included CYPs from 70 fungal and oomycete species. Here we present a new version of FCPD (1.2) with more data and an improved classification scheme.ResultsThe new database contains 22,940 CYPs from 213 species divided into 2,579 clusters and 115 clans. By optimizing the clustering pipeline, we were able to uncover 36 novel clans and to assign 153 orphan CYP families to specific clans. To augment their functional annotation, CYP clusters were mapped to David Nelson's P450 databases, which archive a total of 12,500 manually curated CYPs. Additionally, over 150 clusters were functionally classified based on sequence similarity to experimentally characterized CYPs. Comparative analysis of fungal and oomycete CYPomes revealed cases of both extreme expansion and contraction. The most dramatic expansions in fungi were observed in clans CYP58 and CYP68 (Pezizomycotina), clans CYP5150 and CYP63 (Agaricomycotina), and family CYP509 (Mucoromycotina). Although much of the extraordinary diversity of the pan-fungal CYPome can be attributed to gene duplication and adaptive divergence, our analysis also suggests a few potential horizontal gene transfer events. Updated families and clans can be accessed through the new version of the FCPD database.ConclusionsFCPD version 1.2 provides a systematic and searchable catalogue of 9,550 fungal CYP sequences (292 families) encoded by 108 fungal species and 147 CYP sequences (9 families) encoded by five oomycete species. In comparison to the first version, it offers a more comprehensive clan classification, is fully compatible with Nelson's P450 databases, and has expanded functional categorization. These features will facilitate functional annotation and classification of CYPs encoded by newly sequenced fungal and oomycete genomes. Additionally, the classification system will aid in studying the roles of CYPs in the evolution of fungal adaptation to specific ecological niches.

Project description:Objective: The objective of this study was to test our Viral Quinta Columna Strategy (VQCS), a new biological hypothesis predicting that specific multifunctional virally encoded cationic domains may have the capacity to penetrate human cells and interact with PP2A proteins to deregulate important human intracellular pathways, and may display LL37 cathelicidin-like antagonistic effects against multiple pathogens such as bacteria or viruses. Methods: We comparatively analyzed the host defense properties of adenodiaphorins and of some specific cationic sequences encoded by different viruses using two distinct biological models: U87G, a well-characterized cell tumor model; and a group B Streptococcus agalactiae NEM316 ΔdltA, highly sensitive to LL37 cathelicidin. Results: We found that the adenovirus type 2 E4orf4 is a cell-permeable protein containing a new E4orf464-95 protein transduction domain, named large adenodiaphorin or LadD64-95. Interestingly, the host defense LL37 peptide is the unique cathelicidin in humans. In this context, we also demonstrated that similarly to LL37 LadD64-95, several virally encoded cationic sequences including the C-terminus HIV-1 89.6 Vpr77-92, shorter adenodiaphorins AdD67-84/AdD/69-84/AdD69-83, as well as HIV-2 Tat67-90 and JC polyomavirus small t115-134, displayed similar toxicity against Gram-positive S. agalactiae NEM316 ΔdltA strain. Finally, LadD64-95, adenodiaphorin AdD67-84, AdD69-84, and LL37 and LL17-32 cathelicidin peptides also inhibited the survival of human U87G glioblastoma cells. Conclusion: In this study, we demonstrated that specific cationic sequences encoded by four different viruses displayed antibacterial activities against S. agalactiae NEM316 ΔdltA strain. In addition, HIV-1 Vpr71-92 and adenovirus 2 E4orf464-95, two cationic penetrating sequences that bind PP2A, inhibited the survival of U87G glioblastoma cells. These results illustrate the host defense properties of virally encoded sequences and could represent an initial step for future complete validation of the VQCS hypothesis.

Dataset Information

The first virally encoded cytochrome p450.

Publications

The first virally encoded cytochrome p450.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets