| 研究実績の概要 |
To more precisely link bioactive compounds to their target molecules, we set up the pipeline consisting of the TS (~1,100 strains), HET (~970 strains), WG (~3,000 strains), and MoBY (~960 strains) collections and screened highly bioactive compounds to obtain their chemical genomic profiles. We also isolated ~90 spontaneous drug-resistant mutants for ~40 bioactive compounds and identified mutation sites by next-generation sequencing. This workflow successfully predicted targets of some of the highly bioactive compounds. For example, one compound has a precise HET interaction with FAS1 (fatty acid synthase), and a drug-resistant mutant for the compound shows a non-synonymous SNP in the same gene. Supplementation with fatty acids rescues the compound toxicity, so it is likely that the compound directly targets Fas1.
We planned to construct a drug screening system for the suppressor (SUP) double mutant collection. We tried several pilot experiments using the SUP collection and target-known compounds and found that it did not seem to work properly. However, we confirmed that our chemical genomic pipeline (chemical genomic analysis using the HET, TS, WG and MoBY libraries and drug-resistant mutants) has so far efficiently identified/predicted targets of some of the highly bioactive compounds from the NPDepo library, even without the SUP library.
Furthermore, we developed two scalable computational tools (BEAN-counter and CG-TARGET) to assist in both generating and interpreting chemical genomic interaction profiles as part of our collaboration with University of Minnesota.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We almost established chemical genomic pipeline (chemical genomic analysis using the HET, TS, WG and MoBY libraries and drug-resistant mutants) that has so far efficiently identified/predicted targets of the highly bioactive compounds from the NPDepo library.
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| 今後の研究の推進方策 |
We will fine-adjust the chemical genomic pipeline (chemical genomic analysis using the HET, TS, WG and MoBY libraries and drug-resistant mutants) and using the pipeline we will conduct target identification analysis of the Group A01/A02 collaborators’ compounds. We will also screen highly bioactive compounds from a new set of the NPDepo compounds (~10,000) to do target identification analysis.
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