Metabolic engineering in methanotrophic bacteria

• Methanotrophs have the potential to play a role in our sustainable energy future.
• A system-level understanding of methanotrophic metabolism will lay the groundwork for metabolic engineering to generate value-added products from methane.
• A set of gaps in our fundamental knowledge of methanotrophy make predictive metabolic engineering more difficult, but approaches are available to accommodate the uncertainty.
• A suite of available cultures and tools exist that will facilitate metabolic engineering efforts.
• A set of approaches are suggested that have the potential to increase flux to key precursors for many value-added products.

Methane, as natural gas or biogas, is the least expensive source of carbon for (bio)chemical synthesis. Scalable biological upgrading of this simple alkane to chemicals and fuels can bring new sustainable solutions to a number of industries with large environmental footprints, such as natural gas/petroleum production, landfills, wastewater treatment, and livestock. Microbial biocatalysis with methane as a feedstock has been pursued off and on for almost a half century, with little enduring success. Today, biological engineering and systems biology provide new opportunities for metabolic system modulation and give new optimism to the concept of a methane-based bio-industry. Here we present an overview of the most recent advances pertaining to metabolic engineering of microbial methane utilization. Some ideas concerning metabolic improvements for production of acetyl-CoA and pyruvate, two main precursors for bioconversion, are presented. We also discuss main gaps in the current knowledge of aerobic methane utilization, which must be solved in order to release the full potential of methane-based biosystems.