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Microalgae produce metabolites that could be useful for applications in food, biofuel or fine chemical production. The identification and development of suitable strains require analytical methods that are accurate and allow rapid screening of strains or cultivation conditions. We demonstrate the use of Fourier transform infrared (FT-IR) spectroscopy to screen mutant strains of  Chlamydomonas reinhardtii . These mutants have knockdowns for one or more nutrient starvation response genes, namely  PSR1 ,  SNRK2.1  and  SNRK2.2 . Limitation of nutrients including nitrogen and phosphorus can induce metabolic changes in microalgae, including the accumulation of glycerolipids and starch. By performing multivariate statistical analysis of FT-IR spectra, metabolic variation between different nutrient limitation and non-stressed conditions could be differentiated. A number of mutant strains with similar genetic backgrounds could be distinguished from wild type when grown under specific nutrient limited and replete conditions, demonstrating the sensitivity of FT-IR spectroscopy to detect specific genetic traits. Changes in lipid and carbohydrate between strains and specific nutrient stress treatments were validated by other analytical methods, including liquid chromatography–mass spectrometry for lipidomics. These results demonstrate that the  PSR1  gene is an important determinant of lipid and starch accumulation in response to phosphorus starvation but not nitrogen starvation. However, the  SNRK2.1  and  SNRK2.2  genes are not as important for determining the metabolic response to either nutrient stress. We conclude that FT-IR spectroscopy and chemometric approaches provide a robust method for microalgae screening.   Electronic supplementary material  The online version of this article (doi:10.1007/s11306-015-0878-4) contains supplementary material, which is available to authorized users.

High-throughput metabolic screening of microalgae genetic variation in response to nutrient limitation