Shaping up for commercial production of 1,4-butanediol in Escherichia coli.

A wide range of chemicals, polymers, and advanced materials are produced from oil or natural gas. Many of the technologies to make these chemicals were invented decades ago and although improvements to efficiency have been made, these petrochemical processes raise legitimate concerns regarding their environmental impact and sustainability. Additionally, many petrochemicals suffer from extensive volatility of the fossil fuel feedstock, which prompted efforts to develop more sustainable solutions that can produce the same chemicals from renewable feedstocks in a cost effective and clean manner. Industrial biotechnology provides such a solution applying fermentation-based processes and incorporating metabolically engineered microorganisms to make these chemicals cost competitively. Genomatica has developed metabolic pathways in a bacteria capable of directly producing 1,4-butanediol (BDO) from carbohydrate feedstocks. BDO is a chemical intermediate (~2 M tonnes/year) that goes into a variety of products including automotive, electronics and apparel, and is currently produced commercially through energy-intensive petrochemical processes. Genomatica is utilizing an Escherichia coli strain that produces BDO at high titers, yields and rates that can compete with existing petro processes at scale even at the current low oil and gas prices. Our process-first approach dictated high performance requirements, targeting not only high BDO titers, rates, and yields, but lowering key by-products to simplify and improve downstream processing economics. The result is a robust, genetically stable organism demonstrated at commercial scale. The presentation will discuss recent developments in the strain that were identified using systems biology, pathway enzyme engineering and evolution methods that lead to our industry-ready strain.