Asia’s Scientific Trailblazers: Lee Sang Yup

By tweaking the metabolic pathways of living organisms, Professor Lee Sang Yup is maximizing the synergy between biology and chemistry for the benefit of industry and society.

Lee Sang Yup
Distinguished Professor
Korea Advanced Institute of Science and Technology
South Korea

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AsianScientist (Mar. 29, 2019) – More than just reactions taking place in a test tube, chemistry is the foundation upon which life itself arises. From microscopic bacteria to massive mammals, all living things constantly break down and build up molecules and compounds via a series of coordinated chemical interactions.

By studying how these chemical processes occur in biological systems, scientists have been able to tweak them for industrial applications, a field known as metabolic engineering. For instance, fermentation in bacteria or yeast can be optimized to produce alcohols of varying chain lengths, and photosynthesis in algae can be taken advantage of to create biofuels that are more environmentally friendly.

Helping to build and expand this repertoire of metabolic engineering strategies is Professor Lee Sang Yup of the Korea Advanced Institute of Science and Technology. A chemical engineer by training, Lee has devised multiple approaches to turn organisms into factories of the future, churning out novel compounds with a plethora of uses.

For his expansive research, Lee was recognized with the 2018 Eni Advanced Environmental Solutions Prize, often referred to as the Nobel Prize in the fields of energy and environment. He shares with Asian Scientist Magazine his journey in science and his ambitions for the future.

  1. You trained as a chemical engineer, but you have made a name for yourself in biotechnology. How and why did you make the switch?
  2. I still consider myself a chemical engineer. Chemical engineering is a discipline where one converts low value raw materials to higher value products needed by society.

    When I was an undergraduate student, there was no such subdiscipline as biochemical engineering. As I embarked on my PhD studies, I originally planned to study chemical process design and optimization. However, that theme was not very well covered by the research activities of faculty members back then.

    I thus chose biochemical engineering as my PhD topic, even though I did not know anything about biology or biotechnology at that time. I thought that the use of biology in the context of chemical engineering was exciting and could lead to discoveries that would improve the state of the world.

    During that transition period in my research, I was really fortunate to meet my PhD advisor, Professor Terry Papousakis, who is one of the pioneers in the field of metabolic engineering. Under his supervision, I overcame many problems that I encountered during my PhD study.

  3. Your work on microbial engineering has many applications, from the production of biofuels to chemical synthesis. What do you consider to be your greatest scientific contribution?
  4. I would say that my greatest scientific contribution is the development of a series of platform strategies and tools for the metabolic engineering of microorganisms. In particular, we suggested a subdiscipline of systems metabolic engineering, which integrates all the great tools and strategies of systems biology, synthetic biology and evolutionary engineering, among others, into traditional metabolic engineering.

    These systems metabolic engineering strategies allow for the development of more competitive, high-performance microbial strains for the industrial production of chemicals, fuels and materials from renewable resources. Using these platform strategies, we have developed many different microbial strains capable of producing gasoline and butanol, as well as engineering plastic monomers, polyester monomers and various natural compounds conferring health benefits.

    Also, for the first time, we were able to produce ultra-high-molecular-weight spider-silk proteins that demonstrate stronger-than-steel material properties. We were able to produce even non-natural polymers by direct one-step fermentation, which we think is a game changer for the production of bio-based polymers.

    In January 2019, we published a comprehensive bio-based chemicals map, which some people call the ‘Google Map’ of bio-based chemicals. I think this map and the strategies described therein demonstrate very well what we and others have achieved in the field.

    Professor Lee Sang Yup (leftmost) mentoring students in the lab. Credit: Lee Sang Yup.

  5. What motivates you personally and professionally?
  6. In Asia, teachers and students have a different relationship compared to that in the Western world. My success will be best judged by the successes of my students. I am very fortunate to have met many great students at KAIST. When I see my students become successful, I feel very accomplished.

    As a scientist, my motivation would be to contribute to developing technologies that could create a better world. I think we have developed several important technologies, but we will continue to work hard.

  7. What are you currently working on?
  8. My lab is working on expanding the scope of metabolic engineering. During the last decade, we focused on developing microbial strains for the efficient production of bulk chemicals that can replace petrochemical-derived counterparts.

    Since we have already developed microbial strains capable of producing many important chemicals, fuels and materials, we are now paying more attention to developing strains for the production of chemicals and materials that are considered extremely difficult to synthesize. We have also recently expanded our study of natural compounds and are working on developing future healthcare technologies.

    In addition, I am interested in the use of artificial intelligence to decipher drug-drug interactions and drug-food interactions, and the interrogation of the philosophy of traditional oriental medicine—that is, multi-target and multi-compound therapy. Having said that, we will continue to develop novel metabolic engineering strategies.

  9. What are some innovations in the field of biotechnology that you are most excited about and why?
  10. Some of the important technologies or techniques that immediately come to mind are: super-fast and super-cheap DNA sequencing, genome editing, precision medicine, stem cell engineering, immunotherapy, microbiome engineering for health and agriculture, and, of course, systems metabolic engineering. All these fields are independently and dependently advancing very rapidly.

    Furthermore, data science and machine learning are integrating very rapidly with developments in biotechnology. All of these will lead to the establishment of a more sustainable and healthier society, as well as the development of new industries. The big wave of the fourth industrial revolution is here through the integration of digital, physical and biological worlds.

    Professor Lee Sang Yup (rightmost) and his team at KAIST. Credit: Lee Sang Yup.

  11. How should scientists go about engaging industry partners in their research? What are the benefits of doing so?
  12. We have always been working with industry to some extent. Working with industry is not only good for commercializing technologies developed in the lab, but also great for training students.

    Students will have good opportunities to learn how companies plan projects, perform tasks and make decisions. For me, the rapidly changing strategies in companies give me lots of things to think about when I plan new projects and review existing projects.

  13. What, in your opinion, is the most urgent problem that biotechnology should be addressing?
  14. I think that technologies, including biotechnology, are advancing very rapidly, so I do not think it is necessary to list those technologies that need to be developed more urgently. Rather, it is important to consider the societal impacts of these rapidly advancing technologies so that no one is left out. Therefore, the urgent problems in biotechnology or other fields do not lie with the technology itself, but rather, how we will more smartly and more inclusively use those technologies.

  15. If you were a young graduate student today, what field would you choose to work in?
  16. It would still be biotechnology!

    This article is from a monthly series called Asia’s Scientific Trailblazers. Click here to read other articles in the series.


    Copyright: Asian Scientist Magazine; Photo: Lee Sang Yup.
    Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Jeremy received his PhD from Nanyang Technological University, Singapore, where he studied the role of the tumor microenvironment in cancer progression.

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