METHODS AND ORGANISMS FOR THE GROWTH-COUPLED PRODUCTION OF SUCCINATE

摘要

A non-naturally occurring microorganism comprising one or more gene disruptions encoding an enzyme associated with growth-coupled production of succinate when an activity of the enzyme is reduced, whereby the one or more disruptions confers stable growth-coupled production of succinate onto the non-naturally occurring microorganism is provided. The disruptions can be complete gene disruptions, and the non-naturally occurring organisms can include a variety of prokaryotic or eukaryotic microorganisms. A method of producing a non-naturally occurring microorganism having stable growth-coupled production of succinate is also provided. The method includes: (a) identifying in silico a set of metabolic modifications requiring succinate production during exponential growth, and (b) genetically modifying a microorganism to contain the set of metabolic modifications requiring succinate production.