Science & Technology


Microbes
Microbes able to make valuable chemicals from waste CO2 are at the core of our competitive position. Our microbes are bacteria that grow in darkness as long as CO2 and H2 are provided as carbon and energy sources. Plants and green algae and many bacteria similarly use CO2 as sole carbon source, so this type of metabolism is very widespread in nature. Up to this time, commercial scale biotechnologies for making specialty chemicals, commodity chemicals, antibiotics and other drugs and pharmaceutical proteins have universally used microbes that convert high-energy carbon sources, like glucose or glycerol, into a product. The input high-energy carbon feedstock is broken down inside the cell and built up again to make a product. Our process takes a very simple, low-energy carbon source, CO2 and builds it up to complex and more valuable compounds, just like plants, but without any requirement for light energy.

Optimization of Microbial Productivity 
We are continually improving and developing microbial strains to improve and develop new sustainable technologies. We use a variety of state of the art microbiological and biochemical techniques as well as directed evolution and natural selection.

Synthetic Biology
Recently it has become possible to combine multiple technologies to approach redesign of a microbe with an engineering approach that goes beyond traditional biotechnology. Although the concept is broad, an example of its use for Oakbio would be to combine knowledge of a microbes genome (and all the metabolic pathways that can be defined by the presence of the gene encoding each enzyme), with “metabolomics” (which tells us what metabolites are actually present and in what amounts), and computer-assisted modeling of metabolic pathways (which allows us to test various scenarios of perturbations of the system). We would identify in silico the likely metabolic choke points, then test in silico various hypotheses on how to increase accumulation of the desired compound. For example, we could increase the specific activity of an enzyme in the pathway we want, plus decrease the activity of an enzyme that diverts carbon into a side pathway.

Bioreactor 
Bioreactors that harness the carbon of CO2 gas and the energy of H2 gas using special microbes like those we use at Oakbio have been built and operated at large scale in research facilities. Our bioreactors will require stirring and gas control to feed microbes growing in the liquid or “planktonic” state. The technologies for gas input, control and real-time analysis are well understood, as are the physics and chemistry of gas exchange for CO2 and H2. To reduce costs, we anticipate the opportunity to use retrofitted or decommissioned fermentation reactors. The choice of the bioreactor will be critical to process yield since its geometry and mixing properties are crucial determinants of microbial access to dissolved CO2 and H2 gases. We anticipate generation of important intellectual property on bioreactor design and control, applied specifically to the types of organisms we use. 

Control Systems
Our microbes are grown with inputs of two gases, CO2 and H2, rather than with a typical fermentation feedstock like sucrose or glucose. Control of gas levels in the gas phase and dissolved gas in the culture fluid is critical. The levels of dissolved gases determine the growth rate of our microbes. It is very important for both the highest productivity and for the most efficient use of gas inputs that we monitor and control the dissolved gas concentration in real time. 

Gases
Waste CO2 is generated by most industrial facilities. When released into the atmosphere COcontributes to accumulation of GHGs with potential for long-term effects on world climate. Aside from CO2 emissions from automobiles and other transportation vehicles, chief among the industries contributing to GHG accumulation are coal-fired power plants, diverse chemical manufacturing processes and cement manufacture. Waste industrial gas can contain a high % of CO2, often with significant levels of other important GHGs, such as various oxides of nitrogen and sulfur (NOx and SOx). While many microbes, plants and algae are capable of using CO2 gas as carbon source, only some microbes, such as those we use at Oakbio, are able to grow in the presence of NOx and SOx.

H2 gas is readily available from several sources across the U.S. including"
1. H2 gas pipelines in some states
2. bulk commercial gas supply shipped to our manufacturing site
3. H2 generated on-site from a commercial scale process of “steam reformation”
4. co-location at an existing chemical manufacturing site already generating H2
5. a fully renewable and commercially validated process at point of 
CO2 generation using solar power and water electrolysis.

Analytical Chemistry
We employ a wide range of analytic techniques both in-house and through partnerships. These include GC, GC/MS, LC/MS. HPLC, NMR, expression analysis and gene sequencing.

Product purification
Generally, 50-70% of total production cost is due to downstream processing in classical fermentation processes. For specialty chemicals, recovery costs can range from 10%-50% of total production cost, or even higher for highest technical grades. These comparatively high costs for bioprocess-based manufacture compared with chemical manufacturing are due to the low final concentration of product in the water phase, the complex mixture of cellular materials and chemicals in this phase, and the purity required of the final product. As a bioprocess moves into lower-value and higher-volume chemicals, it is even more important to maximize efficiency, minimize costs and minimize waste byproducts. One solution to this challenge will be to design the bioreactor step and downstream separations as a single, integrated process.