(569a) Ratiometric Tuning of Fatty Acid Biosynthesis

Over the past few decades, growing—if sometimes wavering—concern over climate change has fueled research on the microbial biosynthesis of fatty acids, a promising source of precursors for renewable oleochemicals. Unfortunately, despite a multitude of successful efforts to engineer microorganisms to overproduce fatty acids, general strategies for controlling their titer, product distribution (i.e., chain lengths), and unsaturation fraction remain largely absent. With this presentation, I will discuss our efforts to combine a high-resolution transcriptional control system with a detailed kinetic model to control fatty acid biosynthesis in Escherichia coli. Our results indicate that independent adjustments to the ratios of FAS components can enable fine control over competing biochemical objectives (e.g., titer and chain length) and suggest that the efficient incorporation of heterologous components often requires compositional re-optimization. Broadly, this work provides an experimental framework for adjusting the FAS of E. coli to hit a broad range of production targets (e.g., specific product profiles or fatty acid derivatives).