The manufacture of many things in our everyday lives, from clothing to electronics to vital medical devices, are dependent on petrochemicals derived from fossil fuels like crude oil and natural gas, finite raw materials whose extraction and use are harmful to the environment.
For decades, scientists have searched for ways to wean the chemical industry off petroleum in favor of environmentally friendly and renewable raw materials that can be used to generate commodity chemicals, the chemical building blocks needed to make a variety of soft materials, like plastics.
An Illinois chemistry research team has introduced a powerful new computer-based method that could help speed up the search for new soft materials that can be made from renewable sources rather than petroleum.
They started with a promising alternative path to a more sustainable chemical and materials economy, which is biomanufacturing, the use of living things to produce chemicals. Through metabolic engineering scientists can program microorganisms to produce target molecules to meet society’s chemical needs. Recent developments have demonstrated that a hybrid approach combining traditional chemical synthesis and metabolic engineering methods could lead to a greater diversity in chemicals sourced from microorganisms.
Using their interdisciplinary computational tool, Illinois chemistry professor Nick Jackson and graduate student Shruti Iyer identified chemical pathways between microbial metabolites and valuable chemicals that are typically sourced from fossil fuels to make soft materials. They revealed that many natural compounds found in living organisms share chemical similarities with materials used in everyday products. And they explored ways to expand the range of materials and reactions that could lead to more eco-friendly ways to make soft materials.
Their interdisciplinary computational tool, called the Extended Metabolite Reaction Network (EMRN), could help other scientists explore new targets for biomanufacturing that can be transformed into value-added chemicals within a few synthetic steps. The reaction network works like a navigation map: metabolites naturally produced by microbes serve as staring points, petroleum-derived chemicals are the destinations, and the chemical reactions are the streets that connect them. Along the way, there may be several turns or intermediate molecules between the metabolite and the petrochemical. They tested the EMRN for a maximum of five reaction rounds or turns along the route.
“Our idea was to take the metabolites that are already naturally produced by the organisms and then combine them with chemical reactions that already exist and are established in industry to see if they can produce any useful functional organic materials,” Iyer said.
Into the EMRN they input metabolites naturally produced by three organisms commonly used in metabolic engineering, E. coli, S. cerevisiae (baker’s yeast), and P. aeruginosa, for a total of approximately 5,000 unique molecules that comprise the initial nodes or starting points of the network. Chemical reactions from the USPTO database, one of the largest open access repositories of viable chemical reactions, were input to construct the EMRN.
For each of the five rounds of synthesis, the chemical space created by the EMRN was evaluated for structural complexity and synthetic feasibility. They found that after three rounds of synthesis the structural diversity of product molecules saturates, indicating that three synthetic steps are enough to generate a sufficiently diverse and complex chemical space. Additionally, their analysis shows that the molecules contained within the EMRN comprise 11 out of the 20 biobased platform chemicals identified by the US Department of Energy (DOE).
Furthermore, Iyer and Jackson decided to pay particular attention to the application of the EMRN to chemicals used to make polymers (plastics), organic electronics, and redox active materials. This approach represents a significant departure from current metabolic engineering efforts, which have primarily focused on drug manufacturing or the top priority chemicals identified by the US DOE.
“Synthetic biology and metabolic engineering in these fields focus mostly on making a few commodity chemicals or making drugs, that's where most of the bang for the buck is. They have yet to explore materials applications in any significant detail,” Jackson said.
As a further proof of concept for the utility of the EMRN, they used the Open Macromolecular Genome (OMG), another computational tool built by the Jackson group, to determine if the EMRN can make synthetic routes between metabolites and chemicals used to make plastics. They determined that 89.6% of the molecules represented by the EMRN contain functional groups that are polymerizable, meaning that these building blocks can be reacted into the long chain molecules that make up plastic materials. Molecules in the EMRN also exhibit a variety of motifs with delocalized π-electrons, enabling extended conjugation and promoting π-π stacking interactions which are important characteristics for chemical building blocks used for organic electronics applications.
Moving forward, the researchers hope future reaction networks will improve upon the EMRN by incorporating molecules from a wider range of organisms, by including reactions sourced from biochemical reaction databases, and by taking reaction scalability and green chemistry standards into consideration when choosing chemical routes between molecules.
To contact Nick Jackson: jacksonn@illinois.edu
To contact Shruti Iyer: shrutii2@illinois.edu
The publication entitled “In Silico Exploration of Metabolite-Derived Soft Materials Using a Chemical Reaction Network” can be accessed online at https://doi.org/10.1021/acs.chemmater.5c00163