Sang Yup Lee, Ph.D.

AIMBE College of Fellows Class of 2013
For leading contributions in the development of processes for the bio-based production of chemicals and materials through systems metabolic engineering

Phage-resistant E. coli strains developed to reduce fermentation failure

Via | August 24, 2022

A genome engineering-based systematic strategy for developing phage resistant Escherichia coli strains has been successfully developed through the collaborative efforts of a team led by Professor Sang Yup Lee, Professor Shi Chen, and Professor Lianrong Wang. This study by Xuan Zou et al was published in Nature Communications in August 2022 and featured in the Editors’ Highlights. The collaboration by the School of Pharmaceutical Sciences at Wuhan University, the First Affiliated Hospital of Shenzhen University, and the KAIST Department of Chemical and Biomolecular Engineering has made an important advance in the metabolic engineering and fermentation industry as it solves a big problem of phage infection causing fermentation failure.

Systems metabolic engineering is a highly interdisciplinary field that has made the development of microbial cell factories to produce various bioproducts including chemicals, fuels, and materials possible in a sustainable and environmentally friendly way, mitigating the impact of worldwide resource depletion and climate change. Escherichia coli is one of the most important chassis microbial strains, given its wide applications in the bio-based production of a diverse range of chemicals and materials. With the development of tools and strategies for systems metabolic engineering using E. coli, a highly optimized and well-characterized cell factory will play a crucial role in converting cheap and readily available raw materials into products of great economic and industrial value… Continue reading.

Interactive map of metabolical synthesis of chemicals

Via | August 11, 2022

A research team comprised of Woo Dae Jang, Gi Bae Kim, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST reported an interactive metabolic map of bio-based chemicals. Their research paper “An interactive metabolic map of bio-based chemicals” was published online in Trends in Biotechnology on August 10, 2022.

As a response to rapid climate change and environmental pollution, research on the production of petrochemical products using microorganisms is receiving attention as a sustainable alternative to existing methods of productions. In order to synthesize various chemical substances, materials, and fuel using microorganisms, it is necessary to first construct the biosynthetic pathway toward desired product by exploration and discovery and introduce them into microorganisms. In addition, in order to efficiently synthesize various chemical substances, it is sometimes necessary to employ chemical methods along with bioengineering methods using microorganisms at the same time. For the production of non-native chemicals, novel pathways are designed by recruiting enzymes from heterologous sources or employing enzymes designed though rational engineering, directed evolution, or ab initio design… Continue reading.

Metabolically engineered bacterium produces lutein

Via | August 4, 2022

Lutein is classified as a xanthophyll chemical that is abundant in egg yolk, fruits, and vegetables. It protects the eye from oxidative damage from radiation and reduces the risk of eye diseases including macular degeneration and cataracts. Commercialized products featuring lutein are derived from the extracts of the marigold flower, which is known to harbor abundant amounts of lutein. However, the drawback of lutein production from nature is that it takes a long time to grow and harvest marigold flowers. Furthermore, it requires additional physical and chemical-based extractions with a low yield, which makes it economically unfeasible in terms of productivity. The high cost and low yield of these bioprocesses has made it difficult to readily meet the demand for lutein.

These challenges inspired the metabolic engineers at KAIST, including researchers Dr. Seon Young Park, Ph.D. Candidate Hyunmin Eun, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering. The team’s study was published in Nature Catalysis on August 5, 2022… Continue reading.

3D visualization and quantification of bioplastic PHA in a living bacterial cell

Via Science Daily | July 28, 2021

A research team at KAIST has observed how bioplastic granule is being accumulated in living bacteria cells through 3D holographic microscopy. Their 3D imaging and quantitative analysis of the bioplastic ‘polyhydroxyalkanoate’ (PHA) via optical diffraction tomography provides insights into biosynthesizing sustainable substitutes for petroleum-based plastics.

The bio-degradable polyester polyhydroxyalkanoate (PHA) is being touted as an eco-friendly bioplastic to replace existing synthetic plastics. While carrying similar properties to general-purpose plastics such as polyethylene and polypropylene, PHA can be used in various industrial applications such as container packaging and disposable products… Continue reading.

Deep Learning-Powered ‘DeepEC’ Helps Accurately Understand Enzyme Functions

Via Korea Advanced Institute of Science and Technology | July 9, 2019

A deep learning-powered computational framework, ‘DeepEC,’ will allow the high-quality and high-throughput prediction of enzyme commission numbers, which is essential for the accurate understanding of enzyme functions.

A team of Dr. Jae Yong Ryu, Professor Hyun Uk Kim, and Distinguished Professor Sang Yup Lee at KAIST reported the computational framework powered by deep learning that predicts enzyme commission (EC) numbers with high precision in a high-throughput manner… Continue reading.

Efficiently Producing Fatty Acids and Biofuels from Glucose

Via KAIST | June 19, 2019

Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.

The newly developed strain, created by Distinguished Professor Sang Yup Lee and his team, showed the highest efficiency in producing fatty acids and biodiesels ever reported. It will be expected to serve as a new platform to sustainably produce a wide array of fatty acid-based products from glucose and other carbon substrates… Continue reading.

Engineered Microbial Production of Grape Flavoring

Via KAIST | May 15, 2019

Researchers report a microbial method for producing an artificial grape flavor. Methyl anthranilate (MANT) is a common grape flavoring and odorant compound currently produced through a petroleum-based process that uses large volumes of toxic acid catalysts.

Professor Sang-Yup Lee’s team at the Department of Chemical and Biomolecular Engineering demonstrated production of MANT, a naturally occurring compound, via engineered bacteria. The authors engineered strains of Escherichia coli and Corynebacetrium glutamicum to produce MANT through a plant-based engineered metabolic pathway… Continue reading.

A Comprehensive Metabolic Map for Production of Bio-Based Chemicals

Via Korea Advanced Institute of Science and Technology | January 15, 2019

A KAIST research team completed a metabolic map that charts all available strategies and pathways of chemical reactions that lead to the production of various industrial bio-based chemicals.

The team was led by Distinguished Professor Sang Yup Lee, who has produced high-quality metabolic engineering and systems engineering research for decades, and made the hallmark chemicals map after seven years of studies.

The team presented a very detailed analysis on metabolic engineering for the production of a wide range of industrial chemicals, fuels, and materials. Surveying the current trends in the bio-based production of chemicals in industrial biotechnology, the team thoroughly examined the current status of industrial chemicals produced using biological and/or chemical reactions… Continue reading.

Deep learning predicts drug-drug and drug-food interactions

Via KAIST | April 18, 2018

(Distinguished Professor Sang Yup Lee)

A Korean research team from KAIST developed a computational framework, DeepDDI, that accurately predicts and generates 86 types of drug-drug and drug-food interactions as outputs of human-readable sentences, which allows in-depth understanding of the drug-drug and drug-food interactions.

Drug interactions, including drug-drug interactions (DDIs) and drug-food constituent interactions (DFIs), can trigger unexpected pharmacological effects, including adverse drug events (ADEs), with causal mechanisms often unknown. However, current prediction methods do not provide sufficient details beyond the chance of DDI occurrence, or require detailed drug information often unavailable for DDI prediction.

To tackle this problem, Dr. Jae Yong Ryu, Assistant Professor Hyun Uk Kim and Distinguished Professor Sang Yup Lee, all from the Department of Chemical and Biomolecular Engineering at Korea Advanced Institute of Science and Technology (KAIST), developed a computational framework, named DeepDDI, that accurately predicts 86 DDI types for a given drug pair. The research results were published online in Proceedings of the National Academy of Sciences of the United States of America (PNAS) on April 16, 2018, which is entitled “Deep learning improves prediction of drug-drug and drug-food interactions… Continue reading.

One-Step Production of Aromatic Polyesters by E. coli Strains

Via Korea Advanced Institute of Science and Technology | January 9, 2018

KAIST systems metabolic engineers defined a novel strategy for microbial aromatic polyesters production fused with synthetic biology from renewable biomass. The team of Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering produced aromatic polyesters from Escherichia coli (E. coli) strains by applying microbial fermentation, employing direct microbial fermentation from renewable feedstock carbohydrates.

This is the first report to determine a platform strain of engineered E. coli capable of producing environmentally friendly aromatic polyesters. This engineered E. coli strain, if desired, has the potential to be used as a platform strain capable of producing various high-valued aromatic polyesters from renewable biomass. This research was published in Nature Communications on January 8.

Conventionally, aromatic polyesters boast solid strength and heat stability so that there has been a great deal of interest in fermentative production of aromatic polyesters from renewable non-food biomass, but without success… Continue reading.

KAIST to Participate in the 2017 Davos Forum

Via KAIST | January 17, 2017

KAIST representatives will join high profile, multi-stakeholder dialogues with global leaders across the world to discuss higher education, science, and technological innovation. 
KAIST President Sung-Mo Kang and Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department will participate in the World Economic Forum’s (WEF) Annual Meeting (a.k.a., Davos Forum) on January 17-20, 2017, in Davos-Klosters, Switzerland.
To be held under the theme “Responsive and Responsible Leadership,” the Annual Meeting will offer global leaders from government, business, academia, and civil society a highly interactive platform to address some of the most pressing issues facing the world today, from climate change, economic inequality, to the Fourth Industrial Revolution and its impact on future employment.
On January 18, President Kang will participate in the Global University Leaders Forum, a community of top 26 universities invited from around the world, and will discuss the relevance of higher education in the context of the Fourth Industrial Revolution. He will also share KAIST’s experiences in developing innovative initiatives to bring future-oriented and creative values into its educational and research programs.
On January 19, at the Global Future Council on Production, President Kang will speak about new technologies taking place in traditional production and distribution systems as introduced by the emergence of rapidly evolving technological advancements, and present KAIST’s endeavors to transform those changes into opportunities.
With an eminent group of scientists, including the Director of the US National Science Foundation France A. Córdova and the Editor-in-Chief Philip Campbell of Nature at the Global Science Outlook session, on January 20, President Kang will discuss key challenges for the global science agenda in the year ahead and examine the role of science in formulating public discussions and polices that will have great impact on society and the lives of people.
Currently, Professor Lee is the founding Co-Chair of the WEF’s Global Future Council, an interdisciplinary knowledge network dedicated to promoting innovative thinking on the future. On January 20, he will share his insights at an independent session entitled “World Changing Technology: Biotech and Neurotech,” briefing the audience on the current state of research, development, and commercialization in these fields, as well as explaining how they will contribute to coping with the Fourth Industrial Revolution.
Professor Lee said, “In recent years, we have seen the world become ever more complex, interconnected, and realigned as it is deeply affected by this unprecedented technological innovations, collectively driving the Fourth Industrial Revolution. One pillar of such innovation will take place in biotechnology and neuroscience, which will help us design solutions to many of global problems such as environment, pandemic diseases, aging, healthcare, and previously intractable illnesses.”

Engineered Bacterium Produces 1,3-Diaminopropane, An Important Industrial Chemical

Via KAIST | August 12, 2015

A Korean research team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at the Korea Advanced Institute of Science and Technology (KAIST) reported, for the first time, the production of 1,3-diaminopropane via fermentation of an engineered bacterium.

1,3-Diaminopropane is a three carbon diamine, which has a wide range of industrial applications including epoxy resin and cross-linking agents, as well as precursors for pharmaceuticals, agrochemicals, and organic chemicals. It can also be polymerized with dicarboxylic acids to make polyamides (nylons) for use as engineering plastics, medical materials, and adhesives.

Traditionally, 1,3-diaminopropane is derived from petroleum-based processes. In effort to address critical problems such as the depletion of petroleum and environmental issues inherent to the petroleum-based processes, the research team has developed an Escherichia coli (E. coli) strain capable of producing 1,3-diaminopropane. Using this technology, 1,3-diaminopropane can now be produced from renewable biomass instead of petroleum.

E. coli as found in nature is unable to produce 1,3-diaminopropane. Metabolic engineering, a technology to transform microorganisms into highly efficient microbial cell factories capable of producing chemical compounds of interest, was utilized to engineer the E. coli strain. First, naturally existing metabolic pathways for the biosynthesis of 1,3-diaminopropane were introduced into a virtual cell in silico to determine the most efficient metabolic pathway for the 1,3-diaminopropane production. The metabolic pathway selected was then introduced into an E. coli strain and successfully produced 1,3-diaminopropane for the first time in the world.

Sang Yup Lee Appointed Editorial Board of Journal Cell Systems

Via KAIST | February 13, 2015

Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST has been appointed a member of the founding editorial board of the newly established journal Cell Systems.
Cell Systems will be a sister journal of Cell, one of the three most prestigious scientific journals along with Nature and Science, that publishes a wide range of papers on biological engineering. The first issue of Cell Systems will be published this July.
Cell Systems plans to publish innovative discoveries, reviews of various research instruments, and research findings on integrated and quantified systems in the field of biology.
Professor Lee is a pioneer in metabolic engineering of microorganism with a focus on biopolymers and metabolites production. He is the editor-in-chief of Biotechnology Journal and serves on the editorial board of numerous international journals. He is also a member of the Global Agenda Council of the World Economic Forum and the Presidential Advisory Committee on Science and Technology in Korea.

Sang Yup Lee Calls for Creativity and Collaboration to Solve Global Problems

Via Northwestern McCormick News | January 26, 2015

More than 2 billion people will be age 60 or older by the year 2050, according to a United Nations report. Sang Yup Lee, distinguished professor and dean at the Korea Advanced Institute of Science and Technology (KAIST), shared this stunning statistic during his visit to Northwestern University this week.

“This is scary,” said Lee (PhD ’91). “If seniors are not healthy, then society will be in trouble.”

Hosted by the McCormick School of Engineering’s Dean Seminar Series, Lee discussed several global problems that KAIST is actively working to solve, including the potential economic and social burden of the aging population, the energy crisis, and climate change. “Bio, Nano, and Beyond: Unlocking New Ideas through Collaborative Research” took place Wednesday, January 21 in the Ford Motor Company Engineering Design Center.

Lee said KAIST researchers approach big problems by working collaboratively and thinking creatively. To combat age-related issues such as Parkinson’s disease, for example, biologists, physiologists, chemical engineers, and medical doctors are working together to pioneer new solutions. This interdisciplinary angle has led to finding a new way to deliver light therapy to improve the motor function of animal models with Parkinson’s disease.

“It’s a better solution than administering chemical drugs, which can raise a patient’s tolerance and eventually stop working,” Lee said. “And this work cannot be done solely by medical doctors.”

Buildings at KAIST are designed to facilitate collaboration. Many have open floor plans and no walls, encouraging professors to share lab space and interact more often. The KAIST Institute hosts six interdisciplinary research institutes and six research centers that cover fields ranging from biology, nanotechnology, and information technology to complex system design, optical technology, and disaster studies.

In addition to its 1,500 faculty and staff members, KAIST has 11,000 students who participate in a system called Education 3.0, which promotes creative thinking.

“Professors can do anything in the classroom except for one thing: lecture,” Lee said. “The classroom is for discussion, debate, and group work.”

Sang Yup Lee Appointed Honorary Professor

Via KAIST | November 13, 2014

Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST has been appointed an honorary professor at Beijing University of Chemical Technology (BUCT). Founded in 1958, BUCT is one of the outstanding universities in mainland China, especially in chemistry studies. 
In addition to the Chinese Academy of Sciences (2012), Shanghai Jiao Tong University (2013), Wuhan University (2014), and Hebei University of Technology (2014), this is the fifth honorary professorship Professor Lee has received from higher education institutions in China.
Professor Lee was recognized for his pioneering research in systems metabolic engineering of microorganisms necessary for the development of green chemical industries. He succeeded in producing succinic acid through bacterial fermentation and engineering plastic raw materials in the most effective and economical method for the first time in the world. Professor Lee also developed polylactic acid, a bio-based polymer that allows plastics to be produced through natural and renewable resources, as well as the microbial production of alkanes, an alternative to gasoline that can be produced from fatty acids.
Professor Lee has been actively working as a member of a group of global leaders supported by the World Economic Forum (WEF), serving as the Chairman of the Future of Chemicals, Advanced Materials & Biotechnology, Global Agenda Councils, WEF.

Sang Yup Lee Appointed Honorary Professor

Via KAIST | October 20, 2014

Sang Yup Lee, Distinguished Professor of the Department of Chemical and Biomolecular Engineering at KAIST, has been appointed an honorary professor at Wuhan University in Hubei Province, China. This is the third time that Professor Lee has received an honorary professorship from Chinese academic institutions. The Chinese Academy of Sciences appointed him an honorary professor in 2012, and Shanghai Jia Tong University asked him to serve as an advisory professor in 2013, respectively.

Professor Lee was recognized for his pioneering research in systems metabolic engineering of microorganisms necessary for the development of green chemical industries. He succeeded in producing succinic acid through bacterial fermentation and engineering plastic raw materials in the most effective and economical method for the first time in the world. Professor Lee also developed polylactic acid, a bio-based polymer that allows plastics to be produced through natural and renewable resources, as well as the microbial production of alkanes, an alternative to gasoline that can be produced from fatty acids.

Professor Lee has been actively working as a member of a group of global leaders supported by the World Economic Forum (WEF), serving the Chairman of the Future of Chemicals, Advanced Materials & Biotechnology, Global Agenda Councils, WEF.

Professor Sang Yup Lee Participates in the 2014 Summer Davos Forum

Via KAIST | September 15, 2014

Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering, KAIST, was invited to lead four sessions at the Annual Meeting 2014, the World Economic Forum, also known as the Summer Davos Forum, which was held in Tianjin, China, from September 10th to 12th.

Two of the four sessions Professor Lee participated in were held on September 10th. At the first session entitled “Biotechnology Ecosystem,” he examined with other panelists the future of bioengineering in depth and discussed major policies and industry trends that will be necessary for the development of future biotechnologies.

Professor Lee later attended the “Strategic Shifts in Healthcare” session as a moderator. Issues related to transforming the health industry such as the next-generation genomics, mobile health and telemedicine, and wearable devices and predictive analytics were addressed.

On September 12, Professor Lee joined the “IdeasLab with KAIST” and gave a presentation on nanotechnology. There was a total of ten IdeasLab sessions held at the Summer Davos Forum, and KAIST was the only Korean university ever invited to host this session. In addition to Professor Lee’s presentation, three more presentations were made by KAIST professors on such topics as “Sustainable Energy and Materials” and “Next-generation Semiconductors.”

KAIST Team Produces Gasoline Using E. coli

Via The Korean Herald | September 30, 2013

A group of scientists from the Korea Advanced Institute of Science and Technology has discovered a way to produce gasoline using bacteria for the first time, the school announced.

The finding, published online in the journal Nature on Sunday, could mark a step toward developing new renewable energy.

The research team led by Lee Sang-yup, a professor at the chemical and biomolecular engineering department, used Escherichia coli bacteria that naturally turn sugars into fat to convert fatty acid into oil.

There are a few examples of research succeeding in producing diesel fuel through modified bacteria, but this is the first time a possible substitute for gasoline has been created, the research team said.

Novel Technology to Produce Gasoline by a Metabolically-Engineered Microorganism

Via Science Daily | September 29, 2013

For many decades, we have been relying on fossil resources to produce liquid fuels such as gasoline, diesel, and many industrial and consumer chemicals for daily use. However, increasing strains on natural resources as well as environmental issues including global warming have triggered a strong interest in developing sustainable ways to obtain fuels and chemicals.

Gasoline, the petroleum-derived product that is most widely used as a fuel for transportation, is a mixture of hydrocarbons, additives, and blending agents. The hydrocarbons, called alkanes, consist only of carbon and hydrogen atoms. Gasoline has a combination of straight-chain and branched-chain alkanes (hydrocarbons) consisted of 4-12 carbon atoms linked by direct carbon-carbon bonds.

Previously, through metabolic engineering of Escherichia coli (E. coli), there have been a few research results on the production of long-chain alkanes, which consist of 13-17 carbon atoms, suitable for replacing diesel. However, there has been no report on the microbial production of short-chain alkanes, a possible substitute for gasoline.

In the paper (entitled “Microbial Production of Short-chain Alkanes”) published online in Nature on September 29, a Korean research team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at the Korea Advanced Institute of Science and Technology (KAIST) reported, for the first time, the development of a novel strategy for microbial gasoline production through metabolic engineering of E. coli.

Distinguished Professor Sang-Yup Lee Received 2013 Amgen Biochemical Engineering Award

Via Kaist | April 30, 2013

Previous award winners are world-renowned scholars of biochemical engineering including James Bailey, Michael Shuler and Daniel Wang

KAIST Chemical and Biomolecular Engineering Department’s Professor Sang-Yup Lee has been selected to receive the 2013 Amgen Biochemical Engineering Award. The award ceremony will take place this June at the International Biochemical and Molecular Engineering conference in Beijing, China.

The Amgen Biochemical Engineering Award was established by Amgen, a world renowned American pharmaceutical company, in 1993. Amgen awards leading biochemical engineers every two years. The first Amgen award recipient was James Bailey of the California Institute of Technology (Caltech) in 1993. Since then leading engineers that are sometimes called “founding fathers of biochemical engineering” have received the award including MIT Professor Daniel Wang and Michael Shuler of Cornell University.

Bacteria as Environmentally Friendly Nanoparticle Factories

Via Nanowerk | September 24, 2010

In nature, uni- and multicellular organisms are capable of reducing and accumulating metal ions as detoxification and homeostasis mechanisms when exposed to metal ion solutions. Although the exact mechanisms and identities of microbial proteins associated for metal nanoparticle synthesis are not clear, two cysteine-rich, heavy metal-binding biomolecules, phytochelatin and metallothionein have been relatively well characterized.

Phytochelatins are oligo-glutathione peptides of varying sizes that are synthesized by the protein phytochelatin synthase and that can form metal complexes with cadmium, copper, silver, lead and mercury, while metallothioneins are gene-encoded proteins capable of directly binding metals such as copper, cadmium, and zinc.

This capability of phytochelatin and metallothionein – having different metal binding affinities to various metal ions – has now been employed by researchers for the in vivo biosynthesis of metal nanoparticles by recombinant Escherichia coli.

“The strategy of employing recombinant E. coli expressing metal binding proteins as a nanoparticle factory is generally applicable to the combinatorial synthesis of diverse nanoparticles having a wide range of characteristics, such as optical, electronic, chemical, and magnetic properties” Sang Yup Lee, head of the Metabolic & Biomolecular Engineering National Research Laboratory at KAIST, explains to Nanowerk.