Bacteria have the capacity to produce numerous substances for commercial and industrial applications. Despite this, very few strains are being used on an industrial scale, likely because such “metabolic engineering” requires a hefty investment. Investigators at the Korea Advanced Institute of Science and Technology (KAIST) estimate that it requires anywhere from 50 to 300 person-years of work (!) and several hundred million dollars to engineer strains and implement their use on a large scale. To stream-line the process, KAIST researchers Sang Yup Lee and Hyun Uk Kim recently published
ten strategies to develop industrial microbial strains.
seeks to optimize existing pathways in a cell to more efficiently produce a desired metabolite. Often, this requires some degree of genetic engineering. Strains of E. coli
are already used to produce amino acids such as L-valine, L-lysine, L-arginine, and L-threonine, chemicals such as butanol, and succinic acid, as well as the anti-parasitic drug artemisinin. Microbes can also be used to produce biofuels such as short-chain and fatty alcohols to replace gasoline and diesel.
Lee and Kim’s ten strategies guide researchers from choosing the appropriate host strain, to implementing its use on a commercial scale. They stress first and foremost the need to choose the most economically viable strain, giving special consideration to how easily particular strains can be genetically engineered. When it comes to reconstructing or optimizing metabolic pathways, they recommend the use of “chemo-bioinformatic” tools to construct the most efficient pathways. They also recommend removing any feedback inhibition controls that could diminish the amount of metabolite produced. Another important consideration is how well the bacteria will tolerate the overproduction of certain metabolites, so called “product tolerance”. It may be possible to greatly increase the amount of product made, but this may also inhibit the bacteria’s growth. A final step in the development process is to ensure that engineered strains can be grown on a commercial scale, since oxygen and other nutrients can become limiting factors in large-scale cultures.
According to Lee, “At the moment, the chance of commercializing microbial strains developed in academic labs is very low...We hope that these strategies contribute to improving opportunities to commercializing microbial strains developed in academic labs with drastically reduced costs and efforts, and that a large fraction of petroleum-based processes will be replaced with sustainable bioprocesses”.
, Nature Biotechnology