 Hello and welcome to Top 10 Emerging Technologies, a show from the World Economic Forum that takes a look at the performance of some of the most promising technologies of the last decade. I'm your host, Greta Keenan, and in this episode we'll be talking about microbes that are genetically engineered to produce chemicals and other useful products. The technology behind this greener approach to chemical synthesis, known as systems metabolic engineering, made it onto our list in 2016. To set the scene, let's take a look at this video from one of our events in 2015, where Sanyap Lee, distinguished professor of chemical and biomolecular engineering at Keist, explains the motivation for engineering microbes in this way. In recent years, we have been experiencing increasingly often cases of extreme weather. Very hot, very cold, severe drought, flooding. One of the main causes of such climate change is our heavy dependence on fossil resources, and also chemicals and materials like plastics we need for everyday articles. Can we do something about this to prevent or at least slow down the climate change, where we can use sustainable resource instead of fossil resource, that's biomass, and use microorganisms to convert them into chemicals and fuels. Ultimately in the future, we may not rely on biomass, we can directly use carbon dioxide and water to produce these chemicals and materials we use every day. Here today to tell us more about systems metabolic engineering is Professor Sanyap Lee himself. Hi Sanyap, thanks for joining us. So you've been working in the field of metabolic engineering for over two decades now. Can you briefly explain to us how exactly you'd go about genetically engineering a microbe so that it can produce the products that you're looking for? So we have been engineering microorganisms, in particular bacteria, for the production of various products ranging from bulk chemicals, fine chemicals to plastics, and even drug compounds. So microorganisms, just like us, eat food and run their metabolism to get energy and also synthesize biomolecules needed for their growth and replication. There are thousands of metabolites in their metabolism, obviously, and many of which are interesting products to us. The best known example is ethanol. In general, however, many microorganisms do not produce these products we are interested in with efficiencies high enough for their economically competitiveness level. That's where metabolic engineering comes into play, which can be defined as purposeful modification of cellular metabolism and the regulatory network to overproduce those products of interest or production of even new products which cells have never seen before. Could you just run us through the major benefits of engineering microbes and turning them into these many factories for us, rather than the traditional approaches to chemical synthesis? So fuels, including those suitable for replacing traditional jet fuel, diesel or gasoline, are now all being produced by fermentation of engineered microorganisms. Not only these bulk chemicals or fine chemicals replacing petrochemicals, various natural products which are important for human health and other purposes are being more efficiently produced by fermentation of metabolically engineered microbes, which can replace the tedious and costly step of extracting from plants, insects or animals. More importantly, as the world is trying to move away from using fossil resources to achieve net-zero goal, the number of such bio-based products produced by engineered microorganisms will continue to increase. What have been the major scientific breakthroughs that have got us to this point today where we can genetically modify these microbes to produce the products that we want? I think there are many major scientific breakthroughs, but the major ones include the tools and strategies of genome and gene engineering, and also metabolic flux analysis, which allows systems-level understanding of microbial metabolism and the consequent engineering at the systems level, which we termed systems and metabolic engineering. It sounds like there's clearly a lot of benefit to this approach when it comes to synthesizing chemicals and materials, but how economically viable is it to use this approach compared to traditional methods, and can we scale it up to the levels that we need? The economical biobility of fermentative production of chemicals at large scale is still not great, frankly speaking. Petrochemical industry that has developed to its maturity has an almost perfectly optimal production system that is hard to beat by the more recent bio-based production system. Nonetheless, the economic competitiveness of bio-based production system continues to improve through the development of better microbial cell factories, optimization of fermentation and downstream processes needed for product recovery and purification, and also securing better and inexpensive raw materials for fermentation. Most importantly, it is essential for us to move toward more environmentally friendly production system with net-zero objective, so we do not have many other choices. Some people might be nervous about genetically modifying organisms, and are there any known risks associated with this sort of technology? But scientifically speaking, it should be noted that the metabolically engineered microbes are cultured in a fermenter, which is closed tank system, and are always properly handled so that they will not be released to the environment. Also, if one wishes, these microorganisms can be further engineered so that they cannot survive if they are accidentally released to the environment by using synthetic circuits. Most of all, the microorganisms employed in large-scale fermentation for the production of these chemicals and materials of our interest are non-harmful, and some are those classified as generally recognized as safe, the grass strains, so to me there are nothing much to worry about. Moving further ahead, perhaps to the next five to ten years, what can we expect as a society from systems metabolic engineering? I think systems metabolic engineering will incorporate more and more data science and machine learning together with robotic automation. Then algorithms will definitely come from our brain, but they will be empowered by data science and machine learning including artificial intelligence, and that will be fed to the strain construction robots for automatic cloning, automatic cultivation, and automatic screening of high-performance strain that will allow construction of microbial cell factories much more efficiently with less labor effort. Such biofoundries, which we call, will allow rapid and high throughput strain construction by implementing systems metabolic engineering through the integration of data science and robotic system, and that will be increasingly popular and you'll be cautiously operational in five to ten years to me. Can you envision a future in which we no longer rely on digging up carbon from the ground and instead can rely on these microbe factories to produce the fuels and chemicals and materials that we need? If you look at the mass balance equation of fossil resources we have been relying on, these will eventually go away because we are using them up so rapidly. So bio-based sustainable production system is in general carbon neutral because we use raw material that is biosynthesized using CO2 as a carbon source. So a lot of chemicals and fuels and materials we use nowadays will be produced by biological means and in five to ten years, even more number of different chemicals and materials will be produced in this way, which is using microbial cell factories that has been developed by systems metabolic engineering. Wonderful. Thank you so much Professor Lee and thank you for sharing all your insights over your many decade career in systems metabolic engineering. As we've heard today, systems metabolic engineering, the technology that allows us to produce chemicals and materials from microbes has made significant headway since it made the top ten list in 2016. Scientists can now genetically engineer microbes to produce fuels, medicines and other useful products in a much more sustainable way than before. Using the transition from giant polluting factories to microbe factories will however require significant scale up of systems metabolic engineering, making it cheaper than fossil fuel based approaches. Systems metabolic engineering has the potential to completely disrupt the way we produce materials and chemicals in the next five to ten years and hopefully motivation to slow climate change combined with increased investment in the technology and clear communication around the minimal risks associated with this technology will help get us there. If you enjoyed this episode, please join the conversation on social media and we'll see you next time for another episode of Top Ten Emerging Technologies.