Background:  Amyris is a renewable chemicals company that utilizes advanced synthetic biology techniques to engineer and optimize novel pathways in yeast to produce high value compounds at an industrial scale. In order to cost-effectively manufacture natural, non-native molecules via a biological system, many iterative rounds of metabolic engineering are required to alter the organism's metabolism for optimal production of the desired molecule. One method of improving product yield is to study the altered yeast through a �multi-omics� or a systems biology perspective to identify the metabolic limitations of the engineered host organism.Method: Amyris's BioAnalytics group characterizes metabolically engineered yeast cells through analysis of proteomics, metabolomics, lipidomics, transcriptomics, and physiological factors like growth rate, pathway flux, and viability. When phenotypes of interest are identified in the engineered yeast, for example, low cell viability, one or all of the above techniques is utilized to better understand that phenotype. The data collected from our 'omics' and physiological analyses is consolidated in a 'data warehouse', allowing cross-experimental data access, visualization, and statistical analysis.Results: The multi-omics platform is capable of advancing metabolic engineering through identification of product pathway bottlenecks, monitoring of known toxic metabolites, quality checks to confirm mRNA and protein expression, and characterization of altered cells to direct further strain and process improvements. The results of these analyses have assisted in strain performance through increases in product yield and cell health.Conclusion:   At Amyris, multi-omics analysis is successfully utilized to advance and optimize yeast metabolic engineering for synthetic chemical production.

Advancing rational metabolic engineering in yeast through multi-omic investigations

248th National Meeting (2014)

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