 |
|
 | INDUSTRIAL METABOLIC ENGINEERINGSM
Industrial Metabolic Engineering is a method to generate high quality genetic targets for strain improvement through a random mutational process rather than through theoretical modeling. This approach lets the microorganism do the work of determining the identity of the most important targets, leaving the scientist to do the follow-up work by reverse engineering the organism to determine the science behind the newly acquired trait.
How is industrial metabolic engineering performed?
|
 |
STEP ONE: Choose the right organism and conditions for the knockout library. To speed commercialization, fermentation screening should be performed, if possible, in the organism, medium, and environment that most closely mimics the commercial process.
STEP TWO: Perform High throughput screening in miniature fermentations. The apparatus sits on a bench-top yet has the ability to simultaneously stir the contents of 2,592 wells using 96 well microplates or 13,104 wells using 384 well microplates.
STEP THREE: Find new targets. Industrial Metabolic Engineering leads to knowledge of the rate limiting factor for your process. This information leads to additional rational strain improvement manipulations and process improvements.
STEP FOUR: Design models for further experimentation. Industrial Metabolic Engineering is commercially-driven because it directly results in the generation of higher producing strains, and the knowledge gained leads to further strain optimization through further genetic engineering of the target.
STEP FIVE: Optimize strain improvement technology at the research level. If the mutant strain continues to outperform the parent strain in shake flask and stirred jar formats, then the product is ready for introduction into a commercial pilot plant as a trial (beta) product.
STEP SIX: Commercialize. Transfer the strain improvement technology into a commercial strain and process. Produce more of your final product, increase the profitability of your process with no capital investment needed for additional fermentors.
Advantages of Industrial Metabolic Engineering
Industrial Metabolic Engineering offers a new opportunity to improve existing high-producing strains or to create new "super-producing" strains from scratch. But unlike the super-producing strains currently in use today that came from traditional mutate-and-screen programs, the strains that come from Industrial Metabolic Engineering come with full knowledge of the reason behind the improvements. There are many advantages of the Industrial Metabolic Engineering approach to strain improvement:
1. NO DELETERIOUS MUTATIONS. Strains improved by Industrial Metabolic Engineering can be generated without the introduction of deleterious mutations that may be crippling the industrial strains in use today and keeping yields lower than their theoretical maximum level.
2. UPGRADEABLE STRAIN IMPROVEMENTS. Once a metabolic or genetic target is found by a random transposon insertion, the mutation is not fixed as it is by traditional mutagenesis. Once the mutation is reverse engineered, ways of improving upon the initial mutation can be readily envisioned by further genetic engineering.
3. EASY TO PERFORM THE PROCESS IN THE WILD-TYPE STRAIN. Strain improvement of the wild type strain will uncover multiple first hit improvements by different mechanisms. First hit mutations are always easier to find than are improvements in an already high-producing strain and may still provide useful information.
4. MORE WAYS TO MAKE BETTER STRAINS. Of course mutations that cause strain improvement directly (positive hits) are possible but negative hits (yield worsening mutations) can also be exploited for strain improvement. Negative hits are even more valuable because they generate targets that are not in use by existing super-producing strains.
5. CUSTOMIZED LINEAGES. Layering mutations upon one another in different combinations will create different genetic lineages with metabolic characteristics that can be targeted to a particular type of fermentation process.
|
|
