Progress and Prospects for Metabolic Engineering of Microbes for Biofuels Production

Microbial catalysts are not as malleable as those in synthetic organic chemistry.

The Science

In a review article in the December 3, 2010, issue of Science, DOE Joint Bioenergy Institute director Jay Keasling discusses advances in metabolic engineering and outlines current efforts to develop economical production of biofuel compounds by microbes. Keasling points to recent improvements in DNA sequencing, bioinformatics, and systems biology approaches as key elements enabling recent breakthroughs in microbial production of high value products such as pharmaceuticals. As petroleum prices continue to rise, engineering microbes to synthesize next generation biofuels compatible with existing engines and infrastructure has become more feasible economically. However, more work is needed to provide low cost starting materials from cellulosic biomass, improve genetic tools that allow introduction of metabolic pathways and control elements into microbial genomes, and develop a broader range of host microbes that can produce tailored biofuel compounds and withstand stresses associated with industrial fuel production. Given the rapid pace of recent progress in these areas, Keasling considers the prospects for economical microbial production of biofuels from renewable resources to be very strong.


Metabolic engineering has the potential to produce from simple, readily available, inexpensive starting materials a large number of chemicals that are currently derived from nonrenewable resources or limited natural resources. Microbial production of natural products has been achieved by transferring product-specific enzymes or entire metabolic pathways from rare or genetically intractable organisms to those that can be readily engineered, and production of unnatural specialty chemicals, bulk chemicals, and fuels has been enabled by combining enzymes or pathways from different hosts into a single microorganism and by engineering enzymes to have new function. Whereas existing production routes use well-known, safe, industrial microorganisms, future production schemes may include designer cells that are tailor-made for the desired chemical and production process. In any future, metabolic engineering will soon rival and potentially eclipse synthetic organic chemistry. One area where metabolic engineering has a sizable advantage over synthetic organic chemistry is in the production of natural products, particularly active pharmaceutical ingredients (APIs), some of which are too complex to be chemically synthesized and yet have a value that justifies the cost of developing a genetically engineered microorganism.

Principal Investigator

Jay D. Keasling
Joint BioEnergy Institute
[email protected]

BER Program Manager

Dawn Adin

U.S. Department of Energy, Biological and Environmental Research (SC-33)
Biological Systems Science Division
[email protected]


Keasling, J.D. 2010. “Manufacturing Molecules Through Metabolic Engineering,” Science 330:1355–8.