Industrial Synthetic Biology for Economic Production of Anabolic Compounds

To be cost-competitive, a biological process for producing fuels and commodity chemicals requires high yield and productivity.  This is especially challenging when fermenting sugar into anabolic compounds. Here we describe extensive metabolic engineering of yeast to achieve economical production of farnesene, a commercially important terpene used in a wide variety of applications from cosmetic emollients to advanced biofuels. Industrially relevant titers were initially achieved by overexpressing genes for the yeast mevalonate pathway and a farnesene synthase. Genome scale modeling revealed synthetic networks that potentially could outperform native yeast central metabolism. Two parallel heterologous pathways from glucose to acetyl-CoA were optimized and combined in a top performing strain, nearly doubling the volume of farnesene produced per unit time in our million liter manufacturing plant. More recently we have incorporated a metabolic switch, allowing rapid growth during seed build and a production phase where carbon and energy are directed mostly to product. Concurrent random mutagenesis and screening has introduced both beneficial and deleterious mutations. Some allele replacements have given further improvement. A set of strains has been developed to allow commercial scale production of various compounds.