Bioconversion of natural gas to fuels and chemicals: A symphony of metabolic and chemical engineering

The objective of Intrexon’s natural gas (NG) bioconversion platform is to develop a microbial cell line for industrial-scale production of chemicals, lubricants and fuels from NG, as opposed to sugar.  The low cost and abundant supply of NG are motivators for the development of technologies that convert this highly reduced carbon feedstock into compounds of greater value.  NG bioconversion is an example of a developmental technology that exploits a methanotroph by applying synthetic biology to program it to produce higher value materials of interest, such as alcohol based fuels or terpenes for fuels or chemicals. Currently, the production of both isobutanol and farnesene have been demonstrated.

An effective strain-engineering program requires synergies between metabolic engineering and chemical engineering but, given the nature of the feedstock, this is a critical component for NG bioconversion.  Rapid strain engineering must be effectively supported by low-, medium-, and high-throughput fermentation techniques.  These screening efforts have a higher degree of complexity due to the inherent issues of using a gas feedstock and are thus dependent on the mass transfer rates, partial pressures, and other parameters. In order to better understand the potential limitations of mass transfer in lab scale systems, a model has been developed that relates mass transfer with the quantity of gas present, biomass production and metabolite productivity.  Effective lab scale operations were then established, guided by insights and inferences from the model, to establish screening capacity and capability commensurate with the ability to generate genetic diversity in a non-standard host.