Sang+Yup+Lee
-
A Comprehensive Metabolic Map for Bio-Based Chemicals Production
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.
This comprehensive map is expected to serve as a blueprint for the visual and intuitive inspection of biological and/or chemical reactions for the production of interest from renewable resources. The team also compiled an accompanying poster to visually present the synthetic pathways of chemicals in the context of their microbial metabolism.
As metabolic engineering has become increasing powerful in addressing limited fossil resources, climate change, and other environmental issues, the number of microbially produced chemicals using biomass as a carbon source has increased substantially. The sustainable production of industrial chemicals and materials has been explored with micro-organisms as cell factories and renewable nonfood biomass as raw materials for alternative petroleum. The engineering of these micro-organism has increasingly become more efficient and effective with the help of metabolic engineering – a practice of engineering using the metabolism of living organisms to produce a desired metabolite.
With the establishment of systems metabolic engineering – the integration of metabolic engineering with tools and strategies from systems biology, synthetic biology and evolutionary engineering – the speed at which micro-organisms are being engineered has reached an unparalleled pace.
In order to evaluate the current state at which metabolically engineered micro-organisms can produce a large portfolio of industrial chemicals, the team conducted an extensive review of the literature and mapped them out on a poster. This resulting poster, termed the bio-based chemicals map, presents synthetic pathways for industrial chemicals, which consist of biological and/or chemical reactions.
Industrial chemicals and their production routes are presented in the context of central carbon metabolic pathways as these key metabolites serve as precursors for the chemicals to be produced. The resulting biochemical map allows the detection and analysis of optimal synthetic pathways for a given industrial chemical. In addition to the poster, the authors have compiled a list of chemicals that have successfully been produced using micro-organisms and a list of the corresponding companies producing them commercially. This thorough review of the literature and the accompanying analytical summary will be an important resource for researchers interested in the production of chemicals from renewable biomass sources.
Metabolically engineered micro-organisms have already made a huge contribution toward the sustainable production of chemicals using renewable resources. Professor Lee said he wanted a detailed survey of the current state and capacity of bio-based chemicals production.
“We are so excited that this review and poster will expand further discussion on the production of important chemicals through engineered micro-organisms and also combined biological and chemical means in a more sustainable manner,” he explained.
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biofineries from the Ministry of Science and ICT through the National Research Foundation of Korea.
For further information, Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST ( leesy@kaist.ac.kr , Tel: +82-42-350-3930)
Figure: Bio-based chemicals production through biological and chemical routes. This metabolic map describes representative chemicals that can be produced either by biological and/or chemical means. Red arrows represent chemical routes and blue arrows represent biological routes. Intermediate metabolites in the metabolism of a living organism can serve as a platform toward the production of industrially relevant chemicals. A more comprehensive map presented by the team can be found as a poster in the review.
2019.01.15 View 7432 -
Distinguished Professor Lee Re-Appointed As Co-Chair of the Global Future Council on Biotechnology
(Distinguished Professor Sang Yup Lee)
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering was re-appointed as the co-chair of the Global Future Council on Biotechnology at the World Economic Forum during the annual GFC meeting in Dubai, UAE last week. Elizabeth O’Day, founder and CEO of Olaris Therapeutics, will co-chair the council with him for two years.
Professor Lee served as the inaugural co-chair of the council for two years from 2016 with Professor Feng Zhang from the Broad Institute of MIT and Harvard.
The World Economic Forum’s Global Future Councils on Biotechnology is comprised of 14 members and aims to identify policy opportunities to help accelerate new biotechnological discoveries and applications while guiding dialogue with consumers about their implications.
Professor Lee, who has made significant research breakthroughs in the field of systems metabolic engineering, received the George Washington Carver Award, the PV Danckwerts Memorial Lecture Award, and the Eni Award this year.
2018.11.19 View 3910 -
A Novel Biosensor to Advance Diverse High-Level Production of Microbial Cell Factories
A research group at KAIST presented a novel biosensor which can produce diverse, high-level microbial cell factories. The biosensor monitors the concentration of products and even intermediates when new strains are being developed. This strategy provides a new platform for manufacturing diverse natural products from renewable resources. The team succeeded in creating four natural products of high-level pharmaceutical importance with this strategy.
Malonyl-CoA is a major building block for many value-added chemicals including diverse natural products with pharmaceutical importance. However, due to the low availability of malonyl-CoA in bacteria, many malonyl-CoA-derived natural products have been produced by chemical synthesis or extraction from natural resources that are harmful to the environment and are unsustainable. For the sustainable biological production of malonyl-CoA-derived natural products, increasing the intracellular malonyl-CoA pool is necessary. To this end, the development of a robust and efficient malonyl-CoA biosensor was required to monitor the concentration of intracellular malonyl-CoA abundance as new strains are developed.
Metabolic engineering researchers at KAIST addressed this issue. This research reports the development of a simple and robust malonyl-CoA biosensor by repurposing a type III polyketide synthase (also known as RppA), which produces flaviolin, a colorimetric indicator of malonyl-CoA. Subsequently, the RppA biosensor was used for the rapid and efficient colorimetric screening of gene manipulation targets enabling enhanced malonyl-CoA abundance. The screened beneficial gene targets were employed for the high-level production of four representative natural products derived from malonyl-CoA. Compared with the previous strategies, which were expensive and time-consuming, the new biosensor could be easily applied to industrially relevant bacteria including Escherichia coli, Pseudomonas putida, and Corynebacterium glutamicum to enable a one-step process.
The study employs synthetic small regulatory RNA (sRNA) technology to rapidly and efficiently reduce endogenous target gene expression for improved malonyl-CoA production. The researchers constructed an E. coli genome-scale synthetic sRNA library targeting 1,858 genes covering all major metabolic genes in E. coli. This library was employed with the RppA biosensor to screen for gene targets which are believed to be beneficial for enhancing malonyl-CoA accumulation upon their expression knockdown.
From this colorimetric screening, 14 gene targets were selected, all of which were successful at significantly increasing the production of four natural products (6-methylsalicylic acid, aloesone, resveratrol, and naringenin). Although specific examples are demonstrated in E. coli as a host, the researchers showed that the biosensor is also functional in P. putida and C. glutamicum, industrially important representative gram-negative and gram-positive bacteria, respectively. The malonyl-CoA biosensor developed in this research will serve as an efficient platform for the rapid development of strains capable of producing natural products crucial for the pharmaceutical, chemical, cosmetics, and food industries.
An important aspect of this work is that the high-performance strains constructed in this research were developed rapidly and easily by utilizing the simple approach of colorimetric screening, without involving extensive metabolic engineering approaches. 6-Methylsalicylic acid (an antibiotic) could be produced to the highest titer reported for E. coli, and the microbial production of aloesone (a precursor of aloesin, an anti-inflammatory agent/whitening agent) was achieved for the first time.
“A sustainable process for producing diverse natural products using renewable resources is of great interest. This study represents the development of a robust and efficient malonyl-CoA biosensor generally applicable to a wide range of industrially important bacteria. The capability of this biosensor for screening a large library was demonstrated to show that the rapid and efficient construction of high-performance strains is feasible. This research will be useful for further accelerating the development process of strains capable of producing valuable chemicals to industrially relevant levels,” said Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, who led the research.
This study entitled “Repurposing type III polyketide synthase as a malonyl-CoA biosensor for metabolic engineering in bacteria,” was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on October 02.
PhD students Dongsoo Yang and Won Jun Kim, MS student Shin Hee Ha, research staff Mun Hee Lee, Research Professor Seung Min Yoo, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering and Dr. Jong Hyun Choi of the Applied Microbiology Research Center at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) participated in this research.
Figure: Type III polyketide synthase (RppA) as a malonyl-CoA biosensor. RppA converts five molecules of malonyl-CoA into one molecule of red-colored flaviolin. This schematic diagram shows the overall conceptualization of the malonyl-CoA biosensor by indicating that higher malonyl-CoA abundance leads to higher production and secretion of flaviolin, resulting in a deeper red color of the culture. This system was employed for the enhanced production of four representative natural products (6-methylsalicylic acid, aloesone, resveratrol, and naringenin) from engineered E. coli strains.
2018.10.11 View 9942 -
Engineered E. coli Using Formic Acid and CO2 As a C1-Refinery Platform Strain
(Figure: Formic acid and CO2 assimilation pathways consisting of the reconstructed THF cycle and reverse glycine cleavage reaction. This schematic diagram shows the formic acid and CO2 assimilation procedure through the pathway. Plasmids used in this study and the genetic engineering performed in this study are illustrated.)
A research group at KAIST has developed an engineered E. coli strain that converts formic acid and CO2 to pyruvate and produces cellular energy from formic acid through reconstructed one-carbon pathways. The strategy described in this study provides a new platform for producing value-added chemicals from one-carbon sources.
Formic acid is a carboxylic acid composed of one carbon. Formic acid was produced from CO2 by the chemical method. Recently, the C1 Gas Refinery R&D Center has successfully developed a biological process that produces formic acid from carbon monoxide for the first time. Formic acid is in a liquid state when at room temperature and atmospheric pressure. In addition, it is chemically stable and less toxic, thus, easy to store and transport. Therefore, it can be used as an alternative carbon source in the microbial fermentation process. In order to produce value-added chemicals using formic acid, a metabolic pathway that converts formic acid into cellular molecules composed of multiple carbons is required. However, a metabolic pathway that can efficiently convert formic acid into cellular molecules has not been developed. This acted as an obstacle for the production of value-added chemicals using formic acid
A research group of Ph.D. student Junho Bang and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. This study, entitled “Assimilation of Formic Acid and CO2 by Engineered Escherichia coli Equipped with Reconstructed One-Carbon Assimilation Pathways”, has been published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on September 18.
There has been increasing interest in utilizing formic acid as an alternative carbon source for the production of value-added chemicals. This research reports the development of an engineered E. coli strain that can convert formic acid and CO2 to pyruvate and produce cellular energy from formic acid through the reconstructed one-carbon pathways.
The metabolic pathway that efficiently converts formic acid and CO2 into pyruvate was constructed by the combined use of the tetrahydrofolate cycle and reverse glycine cleavage reaction. The tetrahydrofolate cycle was reconstructed by utilizing Methylobacterium extorquens formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase. The glycine cleavage reaction was reversed by knocking out the repressor gene (gcvR) and overexpressing the gcvTHP genes that encode enzymes related with the glycine cleavage reaction. Formic acid and CO2 conversion to pyruvate was increased via metabolic engineering of the E. coli strain equipped with the one-carbon assimilation pathway.
In addition, in order to reduce glucose consumption and increase formic acid consumption, Candida boidnii formate dehydrogenase was additionally introduced to construct a cellular energy producing pathway from formic acid. This reduces glucose consumption and increases formic acid consumption.
The reconstructed one-carbon pathways can supply cellular molecules and cellular energies from the formic acid and CO2. Thus, the engineered E. coli strain equipped with the formic acid and CO2 assimilation pathway and cellular energy producing pathway from formic acid showed cell growth from formic acid and CO2 without glucose. Cell growth was monitored and 13C isotope analysis was performed to confirm E. coli growth from the formic acid and CO2. It was found that the engineered E. coli strain sustained cell growth from the formic acid and CO2 without glucose.
Professor Lee said, “To construct the C1-refinery system, a platform strain that can convert one-carbon materials to higher carbon materials needs to be developed. In this report, a one-carbon pathway that can efficiently convert formic acid and CO2 to pyruvate was developed and a cellular energy producing pathway from formic acid was introduced. This resulted in an engineered E. coli strain that can efficiently utilize formic acid as a carbon source while glucose consumption was reduced. The reconstructed one-carbon pathways in this research will be useful for the construction of the C1-refinery system.”
This work was supported by the C1 Gas Refinery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016M3D3A1A01913250). For further information: Sang Yup Lee, Distinguished Professor of Chemical and Biomolecular Engineering, KAIST (leesy@kaist.ac.kr, Tel: +82-42-350-3930)
2018.09.18 View 6960 -
Distinguished Professor Sang Yup Lee Announced as the Eni Award Recipient
(Distinguished Professor Sang Yup Lee)
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will be awarded the 2018 Eni Advanced Environmental Solutions Prize in recognition of his innovations in the fields of energy and environment. The award ceremony will take place at the Quirinal Palace, the official residence of Italian President Sergio Mattarella, who will also be attending on October 22.
Eni, an Italian multinational energy corporation established the Eni Award in 2008 to promote technological and research innovation of efficient and sustainable energy resources. The Advanced Environmental Solutions Prize is one of the three categories of the Eni Award. The other two categories are Energy Transition and Energy Frontiers. The Award for Advanced Environmental Solutions recognizes a researcher or group of scientists that has achieved internationally significant R&D results in the field of environmental protection and recovery. The Eni Award is referred to as the Nobel Award in the fields of energy and environment.
Professor Lee, a pioneering leader in systems metabolic engineering was honored with the award for his developing engineered bacteria to produce chemical products, fuels, and non-food biomass materials sustainably and with a low environmental impact. He has leveraged the technology to develop microbial bioprocesses for the sustainable and environmentally friendly production of chemicals, fuels, and materials from non-food renewable biomass.
The award committee said that they considered the following elements in assessing Professor Lee’s achievement: the scientific relevance and the research innovation level; the impact on the energy system in terms of sustainability as well as fairer and broader access to energy; and the adequacy between technological and economic aspects.
Professor Lee, who already won two other distinguished prizes such as the George Washington Carver Award and the PV Danckwerts Memorial Lecture Award this year, said, “I am so glad that the international academic community as well as global industry leaders came to recognize our work that our students and research team has made for decades.”
Dr. Lee’s lab has been producing a lot of chemicals in environmentally friendly ways. Among them, many were biologically produced for the first time and some of these processes have been already commercialized. “We will continue to strive for research outcomes with two objectives: First, to develop bio-based processes suitable for sustainable chemical industry. The other is to contribute to the human healthcare system through development of platform technologies integrating medicine and nutrition,” he added.
2018.09.12 View 7908 -
KAIST Core Technology Fair Accelerates Commercialization
(President Shin makes opening remarks at the KAIST Core Tech Transfer Day in Seoul.)
Technology commercialization is the one of the innovation initiatives KAIST is strongly driving. KAIST showcased six core technologies developed by KAIST research teams during the 2018 KAIST Core Tech Transfer Day on September 10 at Coex in Seoul. More than 300 investors, buyers, and venture capitalists showed up for the fair. This is the second fair organized as one of the strategic innovation initiatives that KAIST is promoting.
Developers of key technologies selected in the fields of bio, nano, AI, and semiconductors presented their distinct technological prowess to the attendees. The technologies are highly relevant for the new industrial environment trends in the Fourth Industrial Revolution.
The 15-member committee comprised of patent attorneys, venture capitalists, and commercialization specialists selected the six core technologies based on their innovativeness, applicability, and marketability. The Office of University-Industry Cooperation (OUIC) plans to offer buyers various services for developing business models, business strategy analysis, and marketing at home and abroad. The six core technologies featured at the fair include:
- Novel technology of a nano patterning platform by Professor Hee Tae Chung from the Department of Chemical and Biomolecular Engineering
- Anticancer therapeutic candidate materials strengthening immune function by Professor Byung Sok Choi from the Department of Chemistry
- Biofuel mass production using micro-organisms by Distinguished Professor Sang-Yup Lee from the Department of Chemical and Biomolecular Engineering
- Compact single-shot hyperspectral camera technology by Min Hyuk Kim from the School of Computing
- AI-powered high speed ultra-high definition upscaling technology by Professor Munchurl Kim from the School of Electrical Engineering - A radiation strong MOSFET device by Hee Chul Lee from the School of Electrical Engineering
President Sung-Chul Shin stressed in his opening remarks that universities should make contributions to economic development through innovation. “Global leading universities are taking an instrumental role in creating new jobs and economic growth with their own technologies. KAIST, as the leading university in Korea, is accelerating the commercialization of technology produced internally to create a meaningful impact for the economy as well as the job market beyond Korea,” he said.
“We are aiming for the global market, not just in Korea. I want KAIST to be a global value creator that can contribute to the betterment of the world through our innovations,” he added.
2018.09.10 View 6614 -
Metabolic Engineering of E. coli for the Secretory Production of Free Haem
Researchers of KAIST have defined a novel strategy for the secretory production of free haem using engineered Escherichia coli (E. coli) strains. They utilized the C5 pathway, the optimized downstream pathways, and the haem exporter to construct a recombinant micro-organism producing extracellular haem using fed-batch fermentation. This is the first report to extracellularly produce haem using engineered E. coli.
This strategy will expedite the efficient production of free haem to serve as a bioavailable iron-supplying agent and an important prosthetic group of multiple hemoproteins for medical uses. This study, led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, was published in Nature Catalysis on Aug. 28.
Haem, an organometallic compound complexed with a ferrous ion, is an essential molecule delivering oxygen in the blood of many animals. It is also a key component of electron transport chains responsible for the respiration of aerobic organisms including diverse bacteria. It is now being widely applied as a bioavailable iron-supplying agent in the healthcare and dietary supplement industries. The demand for haem and the need for the efficient production of this compound continue to grow.
Many previous researchers have attempted to produce free haem using engineered E. coli. However, none of the studies was successful in producing free haem extracellularly, requiring an additional step to extract the accumulated haem from cells for subsequent uses. The secretion of haem in the form of haem peptides or proteins also requires an extraction step to isolate the free haem from the secreted products. Thus, the secretory production of free haem is an important task for the economical production of haem that is suitable for human consumption.
Although some researchers could produce intracellular haem using recombinant E. coli strains, its final titer was extremely low, resulting from the use of sub-optimal metabolic pathways. Furthermore, the addition of the precursors L-glycine and succinate was deemed undesirable for massive industrial production. Thus, it is necessary to construct an optimized haem biosynthetic pathway to enable the efficient production of haem and examine the consequent secretion of free haem.
To address this issue, the KAIST team used multiple strategies to produce extracellular free haem by enhancing its biosynthesis in E. coli. First, the capacities of the C4 and C5 pathways to produce aminolevulinate (ALA) without feeding precursors were examined. After confirming the superior performance of the C5 pathway over the C4 pathway, the metabolic genes of the C5 pathway and downstream pathways for haem biosynthesis were overexpressed. Then, the metabolic pathways were optimized by adjusting the expression levels of the relevant genes and disrupting the putative haem degradation enzyme encoded by the yfeX gene.
Consequently, the resulting engineered strain secreted a significant amount of haem to the medium. Subsequent optimization of the cultivation conditions and the supplementation of nitrogen sources further increased both the titer of the total free haem and the amount of free haem secreted to the medium. Finally, the overexpression of the ccmABC genes encoding the haem exporter further enhanced the production and secretion of haem, producing the highest titer of haem both intracellularly and extracellularly from glucose.
Professor Lee said, “The eco-friendly and sustainable chemical industry is a key global agenda every nation faces. We are conducting research to bio-synthesize high concentrations, high yields, and high productivity in natural products. This novel technology will serve as an opportunity to advance the biochemical industry moving forward.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea. Further Contact: Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea ( leesy@kaist.ac.kr+82-42-350-3930).
2018.08.28 View 6034 -
Distinguished Professor Lee Receives 2018 George Washington Carver Award
(Distinguished Professor Lee)
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will become the 11th recipient of the George Washington Carver Award. The award ceremony will be held during the 2018 Biotechnology Innovation Organization (BIO) World Congress on Industrial Biotechnology from July 16 through 19 at the Pennsylvania Convention Center in Philadelphia.
The annual Carver award recognizes an individual who has made a significant contribution to building the bio-based economy by applying industrial biotechnology to create environmentally sustainable products. It serves as a lasting memorial to the original vision of George Washington Carver who, over a century ago, pioneered bio-based products, materials, and energy derived from renewable agricultural feedstock. Previous recipients include the founder and CEO of POET Jeff Broin, the CEO of DuPont Ellen Kullman, and Professor Gregory Stephanopoulos at MIT.
Professor Lee is a pioneering scholar of systems metabolic engineering, leveraging technology to develop microbial bioprocesses for the sustainable and environment-friendly production of chemicals, fuels, and materials from non-food renewable biomass. He also serves as the dean of the multi-and interdisciplinary research center hub, KAIST Institute.Through his work, Professor Lee has garnered countless achievements, including being one of only 13 people in the world elected as a foreign member of both the National Academy of Sciences USA and the National Academy of Engineering USA.
He has actively promoted the importance of industrial biotechnology through engagement with the public, policymakers, and decision makers around the world. He currently serves as the co-chairman of the Global Future Council on Biotechnology for the World Economic Forum and served as the Chairman of the Emerging Technologies Council and Biotechnology Council for the World Economic Forum.
Upon the award announcement, Dr. Brent Erickson, executive vice president of BIO’s Industrial & Environmental Section lauded Professor Lee’s achievement, saying “Dr. Lee has advanced the bio-based economy by developing innovative products and processes that are sustainable and environmentally friendly. In doing so, he has become a leader in advocating on the importance of industrial biotechnology. His contributions to the advancement of the industry are a continuation of the legacy left behind by George Washington Carver.”
Professor Lee thanked his research team who has worked together for the past few decades, adding, “Industrial biotechnology is becoming increasingly important to help achieve the UN’s Sustainable Development Goals. We should continue to work together to advance the field and establish a solid foundation for the sustainable future.”
The George Washington Carver Award is sponsored by the Iowa Biotechnology Association. Joe Hrdlicka, executive director of the Iowa Biotechnology Association, said, “Dr. Sang Yup Lee’s significant contributions to the advancement of industrial biotechnology make him the perfect recipient for the George Washington Carver Award. Having published more than 575 peer-reviewed papers, contributed to 82 books, and holding 636 patents, the culmination of Dr. Lee’s work has led to the establishment of sustainable systems for bio-based production of chemicals, fuels, and materials, thus reducing environmental impact and improving quality of life for all.”
2018.07.12 View 12048 -
P.V. Danckwerts Memorial Lecture Awards Distinguished Professor Lee
(Distinguished Professor Sang Yup Lee)
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering was selected as the awardee of the 2018 P.V. Danckwerts Memorial Lecture.
Professor Lee was named the recipient in recognition of his distinguished achievements developing innovative eco-friendly and sustainable chemical materials by applying metabolic engineering. The award is co-sponsored by the Chemical Engineering Science, the Institute of Chemical Engineers, the American Institute of Chemical Engineers, and the European Federation of Chemical Engineering.
The award ceremony and Professor Lee’s lecture will be held at the annual meeting of the American Institute of Chemical Engineers in October in Pittsburgh, PA in the US. He will give a lecture titled “Biotechnology to Help Achieve the UN’s Sustainable Development Goals.”
The P.V. Danckwerts Lecture was established in 1985 in honor of Professor Peter V. Danckwerts at the University of Cambridge who made significant contributions to the chemical engineering field. Professor Danckwerts served as executive editor of the Chemical Engineering Science and the president of the Institute of Chemical Engineers.
Professor Lee, currently the dean of KAIST Institutes, a multi-and interdisciplinary convergence research center, is taking the lead in biotechnology, especially in the field of metabolic engineering.
Professor Lee’s research team’s novel approaches have been gaining notable attention in the sustainable chemical engineering field and future health care innovations. His team recently presented research on drug-drug and drug-food interactions by using AI, a recombinant E.coli strain that biosynthesizes 60 different nanomaterials covering 35 elements on the periodic table, bio-degradable aromatic polymer’s enzyme production, and a molecular mechanism for PET degradation.
With this award, Professor Lee joined other prominent recipients including Dr. Neal Amundson at the University of Houston, the late Professor Octave Levenspiel at Oregon State University, and Professor Rutherford Aris at the University of Minnesota. Professor Lee is the second Asian recipient, following Dr. Mooson Kwauk at the Institute of Process Engineering of the Chinese Academy of Sciences who won the lecture award in 1989.
2018.06.18 View 5943 -
Recombinant E. Coli As a Biofactory for the Biosynthesis of Diverse Nanomaterials
(Distinguished Professor Lee and PhD candidate Choi)
A metabolic research group at KAIST and Chung-Ang University in Korea has developed a recombinant E. coli strain that biosynthesizes 60 different nanomaterials covering 35 elements on the periodic table. Among the elements, the team could biosynthesize 33 novel nanomaterials for the first time, advancing the forward design of nanomaterials through the biosynthesis of various single and multi-elements.
The study analyzed the nanomaterial biosynthesis conditions using a Pourbaix diagram to predict the producibility and crystallinity. Researchers studied a Pourbaix diagram to predict the stable chemical species of each element for nanomaterial biosynthesis at varying levels of reduction potential (Eh) and pH. Based on the Pourbaix diagram analyses, the initial pH of the reaction was changed from 6.5 to 7.5, resulting in the biosynthesis of various crystalline nanomaterials that were previously amorphous or not synthesized.
This strategy was extended to biosynthesize multi-element nanomaterials. Various single and multi-element nanomaterials biosynthesized in this research can potentially serve as new and novel nanomaterials for industrial applications such as catalysts, chemical sensors, biosensors, bioimaging, drug delivery, and cancer therapy.
A research group consisting of PhD candidate Yoojin Choi, Associate Professor Doh Chang Lee, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST and Associate Professor Tae Jung Park of the Department of Chemistry at Chung-Ang University reported the synthesis. This study, entitled “Recombinant Escherichia coli as a biofactory for various single- and multi-element nanomaterials,” was published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on May 21.
A recent successful biosynthesis of nanomaterials under mild conditions without requiring physical and chemical treatments has triggered the exploration of the full biosynthesis capacity of a biological system for producing a diverse range of nanomaterials as well as for understanding biosynthesis mechanisms for crystalline versus amorphous nanomaterials.
There has been increased interest in synthesizing various nanomaterials that have not yet been synthesized for various applications including semiconducting materials, enhanced solar cells, biomedical materials, and many others. This research reports the construction of a recombinant E. coli strain that co-expresses metallothionein, a metal binding protein, and phytochelatin synthase that synthesizes the metal-binding peptide phytochelatin for the biosynthesis of various nanomaterials. Subsequently, an E. coli strain was engineered to produce a diverse range of nanomaterials, including those never biosynthesized before, by using 35 individual elements from the periodic table and also by combining multi-elements.
Distinguished Professor Lee said, “An environmentally-friendly and sustainable process is of much interest for producing nanomaterials by not only chemical and physical methods but biological synthesis. Moreover, there has been much attention paid to producing diverse and novel nanomaterials for new industrial applications. This is the first report to predict the biosynthesis of various nanomaterials, by far the largest number of various single- and multi-elements nanomaterials. The strategies used for nanomaterial biosynthesis in this research will be useful for further diversifying the portfolio of nanomaterials that can be manufactured.”
Figure: The biosynthesis of diverse nanomaterials using recombinant E. coli. This schematic diagram shows the overall conceptualization of the biosynthesis of various single and multi-element nanomaterials using recombinant E. coli under incubation with corresponding elemental precursors. The 35 elements that were tested to biosynthesize nanomaterials are shown in black circles on the periodic table.
2018.05.23 View 11693 -
Cross-Generation Collaborative Labs Open
KAIST opened two cross-generation collaborative labs last month. This novel approach will pair up senior and junior faculty members for sustaining research and academic achievements even after the senior researcher retires.
This is one of the Vision 2031 innovation initiatives established to extend the spectrum of knowledge and research competitiveness. The selected labs will be funded for five years and the funding will be extended if necessary. KAIST will continue to select new labs every year.
A five-member selection committee including the Nobel Laureates Professor Klaus Von Klitzing at the Max-Planck Institute for Solid State Research and Dr. Kurt Wüthrich from ETH Zürich selected the first two labs with senior-junior pairs in March.
(Two renowned scholars' Cross-Generation Collaborative Labs which opened last month.
Distinguished Professor Lee's lab (above) andChair Professor Sung's lab)
Both labs are run by world-renowned scholars: the Systems Metabolic Engineering and Systems Healthcare Laboratory headed by Distinguished Professor Sang-Yup Lee in the Department of Chemical and Biomolecular Engineering and the Acousto-Microfluidics Research Center for Next-Generation Healthcare led by Chair Professor Hyung Jin Sung in the Department of Mechanical Engineering.
Distinguished Professor Lee will be teamed up with Professor Hyun Uk Kim, and their lab aims to mass produce new eco-friendly chemical materials as well as higher-value-added materials which will be used for medicine. The new platform technologies created in the lab are expected to provide information which will benefit human healthcare.
Meanwhile, the Acousto-Microfluidics Research Center for Next-Generation Healthcare will team up with Professors Hyoungsoo Kim and Yeunwoo Cho under Chair Professor Sung. The lab will conduct research on controlling fluids and objects exquisitely on a micro-nano scale by using high-frequency acoustic waves. The lab plans to develop a next-generation healthcare platform for customized diagnoses as well as disease treatment.
KAIST President Sung-Chul Shin, who introduced this novel idea in his research innovation initiative, said that he hopes the Cross-Generation Collaborative Labs will contribute to honoring senior scholars’ research legacies and passing knowledge down to junior researchers in order to further develop their academic achievements. He said, “I sincerely hope the labs will make numerous research breakthroughs in the very near future.”
2018.05.03 View 12084 -
Deep Learning Predicts Drug-Drug and Drug-Food Interactions
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.”
DeepDDI takes structural information and names of two drugs in pair as inputs, and predicts relevant DDI types for the input drug pair. DeepDDI uses deep neural network to predict 86 DDI types with a mean accuracy of 92.4% using the DrugBank gold standard DDI dataset covering 192,284 DDIs contributed by 191,878 drug pairs. Very importantly, DDI types predicted by DeepDDI are generated in the form of human-readable sentences as outputs, which describe changes in pharmacological effects and/or the risk of ADEs as a result of the interaction between two drugs in pair. For example, DeepDDI output sentences describing potential interactions between oxycodone (opioid pain medication) and atazanavir (antiretroviral medication) were generated as follows: “The metabolism of Oxycodone can be decreased when combined with Atazanavir”; and “The risk or severity of adverse effects can be increased when Oxycodone is combined with Atazanavir”. By doing this, DeepDDI can provide more specific information on drug interactions beyond the occurrence chance of DDIs or ADEs typically reported to date.
DeepDDI was first used to predict DDI types of 2,329,561 drug pairs from all possible combinations of 2,159 approved drugs, from which DDI types of 487,632 drug pairs were newly predicted. Also, DeepDDI can be used to suggest which drug or food to avoid during medication in order to minimize the chance of adverse drug events or optimize the drug efficacy. To this end, DeepDDI was used to suggest potential causal mechanisms for the reported ADEs of 9,284 drug pairs, and also predict alternative drug candidates for 62,707 drug pairs having negative health effects to keep only the beneficial effects. Furthermore, DeepDDI was applied to 3,288,157 drug-food constituent pairs (2,159 approved drugs and 1,523 well-characterized food constituents) to predict DFIs. The effects of 256 food constituents on pharmacological effects of interacting drugs and bioactivities of 149 food constituents were also finally predicted. All these prediction results can be useful if an individual is taking medications for a specific (chronic) disease such as hypertension or diabetes mellitus type 2.
Distinguished Professor Sang Yup Lee said, “We have developed a platform technology DeepDDI that will allow precision medicine in the era of Fourth Industrial Revolution. DeepDDI can serve to provide important information on drug prescription and dietary suggestions while taking certain drugs to maximize health benefits and ultimately help maintain a healthy life in this aging society.”
Figure 1. Overall scheme of Deep DDDI and prediction of food constituents that reduce the in vivo concentration of approved drugs
2018.04.18 View 12112