Abstract
Chemical biology, the interfacial discipline of using small molecules as probes to investigate biology, is a powerful approach of developing specific, rapidly acting tools that can be applied across organisms. The single-celled alga Chlamydomonas reinhardtii is an excellent model system because of its photosynthetic ability, cilia-related motility and simple genetics. We report the results of an automated fitness screen of 5,445 small molecules and subsequent assays on motility/phototaxis and photosynthesis. Cheminformatic analysis revealed active core structures and was used to construct a naïve Bayes model that successfully predicts algal bioactive compounds.
Highlights
Chemical biology uses small molecules to study and manipulate biological systems
We demonstrate the effectiveness of Chlamydomonas as a chemical biology subject, and define and model physiochemical parameters that characterize small molecule activity on Chlamydomonas
Chlamydomonas as a chemical biology model To screen for small molecules that inhibit the growth of Chlamydomonas we performed an 80-hour fitness assay (Figure 1a)
Summary
Chemical biology uses small molecules to study and manipulate biological systems (reviewed in [1]). The approach is analogous to genetic manipulation to produce an observable phenotype (reviewed in [2]). The single-celled green alga Chlamydomonas reinhardtii, often referred to as the ‘green yeast’ [3], is a powerful model organism that can be manipulated, with straightforward genetics and a wide range of informative phenotypes. Our experience with yeast chemical perturbation has shown that data derived from simple fitness screens are quite valuable, with growth being the ultimate ‘integrative phenotype’. Information at this stage can be invaluable for facilitating genetic and genomic approaches to determine possible mechanisms of action of small molecule growth inhibitors [27,28]
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