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KAIST Research Team Creates the Scent of Jasmine from Microorganisms
The fragrance of jasmine and ylang-ylang, used widely in the manufacturing of cosmetics, foods, and beverages, can be produced by direct extraction from their respective flowers. In reality, this makes it difficult for production to meet demand, so companies use benzyl acetate, a major aromatic component of the two fragrances that is chemically synthesized from raw materials derived from petroleum.
On February 26, a KAIST research team led by Research Professor Kyeong Rok Choi from the BioProcess Engineering Research Center and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering revealed the development of the first microbial process to effectively produce benzyl acetate, an industrially useful compound, from renewable carbon sources such as glucose. The results were published in their paper titled “A microbial process for the production of benzyl acetate”.
< Figure 1. Production of benzyl acetate through co-culture of upstream and downstream strains harboring the benzoic acid-dependent pathway. >
The team, led by Distinguished Professor Lee, aimed to produce benzyl acetate through an environmentally friendly and sustainable method, and developed an Escherichia coli strand to convert glucose into benzyl acetate through system metabolic engineering*.
*System metabolic engineering: a field of research founded by Distinguished Professor Lee to effectively develop microbial cell plants, a core component of the bio-industry that will replace the existing chemical industry, which is highly dependent on petroleum.
The research team developed a metabolic pathway that biosynthesizes benzyl acetate from benzoic acid derived from glucose, and successfully produced benzyl acetate by co-culturing** the strain.
**co-culture: simultaneously synthesizing two or more types of microorganisms in a mixture
However, it has been confirmed that the enzyme used to convert benzoic acid into benzyl acetate in this co-culturing technique acts non-specifically on an intermediate product during benzoic acid biosynthesis, producing a by-product called cinnamyl acetate. This process consumes the intermediate product needed for benzoic acid biosynthesis, thereby reducing the production efficiency of the target compound, benzyl acetate.
To overcome this problem, Distinguished Professor Lee and his team devised a delayed co-culture method, where they first produced benzoic acid in the earlier stages of fermentation by only culturing the top strain that produces benzoic acid from glucose, and later inoculated the bottom strain to convert the accumulated benzoic acid in the culture medium into benzyl acetate.
By applying this co-culture technique, the team suppressed the formation of by-products without further strain improvement or applying additional enzymes, and multiplied the concentration of the target compound by 10 times, producing 2.2 g/L of benzyl acetate. In addition, the team confirmed its potential for the commercial production of benzyl acetate through a technical economic analysis on this microbial process.
< Figure 2. Delayed co-culture of the Bn1 and Bn-BnAc3 strains for improved production of benzyl acetate through the benzoic acid-independent pathway.>
Research Professor Keyong Rok Choi, who was the first author of this paper, said, “This work is significant in that we have developed an effective microbial process to produce the industrially useful compound benzyl acetate, and also in that we have suggested a new approach to overcome the target chemical efficiency diminution and by-product formation issues caused commonly through non-specific enzyme activities during metabolic engineering.”
Distinguished Professor Lee said, “If we can increase the variety and number of microbial processes that produce useful chemicals through sustainable methods and at the same time develop effective strategies to solve chronic and inevitable problems that arise during microbial strain development, we will be able to accelerate the transition from the petrochemical industry into the eco-friendly and sustainable bio-industry.
This work was published online in Nature Chemical Engineering, issued by Nature.
This research was supported by the ‘Implementation of Intelligent Cell Factory Technology (PI: Distinguished Professor Sang Yup Lee) Project by the Ministry of Science and ICT, and the ‘Development of Protein Production Technology from Inorganic Substances through Microbiological Metabolic System Control’ (PI: Research Professor Kyeong Rok Choi) by the Agricultural Microbiological Project Group at the Rural Development Administration.
2024.03.05 View 3444 -
KAIST & LG U+ Team Up for Quantum Computing Solution for Ultra-Space 6G Satellite Networking
KAIST quantum computer scientists have optimized ultra-space 6G Low-Earth Orbit (LEO) satellite networking, finding the shortest path to transfer data from a city to another place via multi-satellite hops.
The research team led by Professor June-Koo Kevin Rhee and Professor Dongsu Han in partnership with LG U+ verified the possibility of ultra-performance and precision communication with satellite networks using D-Wave, the first commercialized quantum computer.
Satellite network optimization has remained challenging since the network needs to be reconfigured whenever satellites approach other satellites within the connection range in a three-dimensional space. Moreover, LEO satellites orbiting at 200~2000 km above the Earth change their positions dynamically, whereas Geo-Stationary Orbit (GSO) satellites do not change their positions. Thus, LEO satellite network optimization needs to be solved in real time.
The research groups formulated the problem as a Quadratic Unconstrained Binary Optimization (QUBO) problem and managed to solve the problem, incorporating the connectivity and link distance limits as the constraints.
The proposed optimization algorithm is reported to be much more efficient in terms of hop counts and path length than previously reported studies using classical solutions. These results verify that a satellite network can provide ultra-performance (over 1Gbps user-perceived speed), and ultra-precision (less than 5ms end-to-end latency) network services, which are comparable to terrestrial communication.
Once QUBO is applied, “ultra-space networking” is expected to be realized with 6G. Researchers said that an ultra-space network provides communication services for an object moving at up to 10 km altitude with an extreme speed (~ 1000 km/h). Optimized LEO satellite networks can provide 6G communication services to currently unavailable areas such as air flights and deserts.
Professor Rhee, who is also the CEO of Qunova Computing, noted, “Collaboration with LG U+ was meaningful as we were able to find an industrial application for a quantum computer. We look forward to more quantum application research on real problems such as in communications, drug and material discovery, logistics, and fintech industries.”
2022.06.17 View 6263 -
Natural Rainbow Colorants Microbially Produced
Integrated strategies of systems metabolic engineering and membrane engineering led to the production of natural rainbow colorants comprising seven natural colorants from bacteria for the first time
A research group at KAIST has engineered bacterial strains capable of producing three carotenoids and four violacein derivatives, completing the seven colors in the rainbow spectrum. The research team integrated systems metabolic engineering and membrane engineering strategies for the production of seven natural rainbow colorants in engineered Escherichia coli strains. The strategies will be also useful for the efficient production of other industrially important natural products used in the food, pharmaceutical, and cosmetic industries.
Colorants are widely used in our lives and are directly related to human health when we eat food additives and wear cosmetics. However, most of these colorants are made from petroleum, causing unexpected side effects and health problems. Furthermore, they raise environmental concerns such as water pollution from dyeing fabric in the textiles industry. For these reasons, the demand for the production of natural colorants using microorganisms has increased, but could not be readily realized due to the high cost and low yield of the bioprocesses.
These challenges inspired the metabolic engineers at KAIST including researchers Dr. Dongsoo Yang and Dr. Seon Young Park, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering. The team reported the study entitled “Production of rainbow colorants by metabolically engineered Escherichia coli” in Advanced Science online on May 5. It was selected as the journal cover of the July 7 issue.
This research reports for the first time the production of rainbow colorants comprising three carotenoids and four violacein derivatives from glucose or glycerol via systems metabolic engineering and membrane engineering. The research group focused on the production of hydrophobic natural colorants useful for lipophilic food and dyeing garments. First, using systems metabolic engineering, which is an integrated technology to engineer the metabolism of a microorganism, three carotenoids comprising astaxanthin (red), -carotene (orange), and zeaxanthin (yellow), and four violacein derivatives comprising proviolacein (green), prodeoxyviolacein (blue), violacein (navy), and deoxyviolacein (purple) could be produced. Thus, the production of natural colorants covering the complete rainbow spectrum was achieved.
When hydrophobic colorants are produced from microorganisms, the colorants are accumulated inside the cell. As the accumulation capacity is limited, the hydrophobic colorants could not be produced with concentrations higher than the limit. In this regard, the researchers engineered the cell morphology and generated inner-membrane vesicles (spherical membranous structures) to increase the intracellular capacity for accumulating the natural colorants. To further promote production, the researchers generated outer-membrane vesicles to secrete the natural colorants, thus succeeding in efficiently producing all of seven rainbow colorants. It was even more impressive that the production of natural green and navy colorants was achieved for the first time.
“The production of the seven natural rainbow colorants that can replace the current petroleum-based synthetic colorants was achieved for the first time,” said Dr. Dongsoo Yang. He explained that another important point of the research is that integrated metabolic engineering strategies developed from this study can be generally applicable for the efficient production of other natural products useful as pharmaceuticals or nutraceuticals. “As maintaining good health in an aging society is becoming increasingly important, we expect that the technology and strategies developed here will play pivotal roles in producing other valuable natural products of medical or nutritional importance,” explained Distinguished Professor Lee.
This work was supported by the "Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ01550602)" Rural Development Administration, Republic of Korea.
-Publication:Dongsoo Yang, Seon Young Park, and Sang Yup Lee. Production of rainbow colorants by metabolically engineered Escherichia coli. Advanced Science, 2100743.
-Profile Distinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr
Department of Chemical and Biomolecular EngineeringKAIST
2021.06.09 View 8762 -
Visualization of Functional Components to Characterize Optimal Composite Electrodes
Researchers have developed a visualization method that will determine the distribution of components in battery electrodes using atomic force microscopy. The method provides insights into the optimal conditions of composite electrodes and takes us one step closer to being able to manufacture next-generation all-solid-state batteries.
Lithium-ion batteries are widely used in smart devices and vehicles. However, their flammability makes them a safety concern, arising from potential leakage of liquid electrolytes.
All-solid-state lithium ion batteries have emerged as an alternative because of their better safety and wider electrochemical stability. Despite their advantages, all-solid-state lithium ion batteries still have drawbacks such as limited ion conductivity, insufficient contact areas, and high interfacial resistance between the electrode and solid electrolyte.
To solve these issues, studies have been conducted on composite electrodes in which lithium ion conducting additives are dispersed as a medium to provide ion conductive paths at the interface and increase the overall ionic conductivity.
It is very important to identify the shape and distribution of the components used in active materials, ion conductors, binders, and conductive additives on a microscopic scale for significantly improving the battery operation performance.
The developed method is able to distinguish regions of each component based on detected signal sensitivity, by using various modes of atomic force microscopy on a multiscale basis, including electrochemical strain microscopy and lateral force microscopy.
For this research project, both conventional electrodes and composite electrodes were tested, and the results were compared. Individual regions were distinguished and nanoscale correlation between ion reactivity distribution and friction force distribution within a single region was determined to examine the effect of the distribution of binder on the electrochemical strain.
The research team explored the electrochemical strain microscopy amplitude/phase and lateral force microscopy friction force dependence on the AC drive voltage and the tip loading force, and used their sensitivities as markers for each component in the composite anode.
This method allows for direct multiscale observation of the composite electrode in ambient condition, distinguishing various components and measuring their properties simultaneously.
Lead author Dr. Hongjun Kim said, “It is easy to prepare the test sample for observation while providing much higher spatial resolution and intensity resolution for detected signals.” He added, “The method also has the advantage of providing 3D surface morphology information for the observed specimens.”
Professor Seungbum Hong from the Department of Material Sciences and Engineering said, “This analytical technique using atomic force microscopy will be useful for quantitatively understanding what role each component of a composite material plays in the final properties.”
“Our method not only will suggest the new direction for next-generation all-solid-state battery design on a multiscale basis but also lay the groundwork for innovation in the manufacturing process of other electrochemical materials.”
This study is published in ACS Applied Energy Materials and supported by the Big Science Research and Development Project under the Ministry of Science and ICT and the National Research Foundation of Korea, the Basic Research Project under the Wearable Platform Materials Technology Center, and KAIST Global Singularity Research Program for 2019 and 2020.
Publication:Kim, H, et al. (2020) ‘Visualization of Functional Components in a Lithium Silicon Titanium Phosphate-Natural Graphite Composite Anode’. ACS Applied Energy Materials, Volume 3, Issue 4, pp. 3253-3261. Available online at https://doi.org/10.1021/acsaem.9b02045
Profile:
Seungbum Hong
Professor
seungbum@kaist.ac.kr
http://mii.kaist.ac.kr/
Materials Imaging and Integration Laboratory
Department of Material Sciences and Engineering
KAIST
2020.05.22 View 8658 -
Wearable Strain Sensor Using Light Transmittance Helps Measure Physical Signals Better
KAIST researchers have developed a novel wearable strain sensor based on the modulation of optical transmittance of a carbon nanotube (CNT)-embedded elastomer. The sensor is capable of sensitive, stable, and continuous measurement of physical signals. This technology, featured in the March 4th issue of ACS Applied Materials & Interfaces as a front cover article, shows great potential for the detection of subtle human motions and the real-time monitoring of body postures for healthcare applications.
A wearable strain sensor must have high sensitivity, flexibility, and stretchability, as well as low cost. Those used especially for health monitoring should also be tied to long-term solid performance, and be environmentally stable. Various stretchable strain sensors based on piezo-resistive and capacitive principles have been developed to meet all these requirements.
Conventional piezo-resistive strain sensors using functional nanomaterials, including CNTs as the most common example, have shown high sensitivity and great sensing performance. However, they suffer from poor long-term stability and linearity, as well as considerable signal hysteresis. As an alternative, piezo-capacitive strain sensors with better stability, lower hysteresis, and higher stretchability have been suggested. But due to the fact that piezo-capacitive strain sensors exhibit limited sensitivity and strong electromagnetic interference caused by the conductive objects in the surrounding environment, these conventional stretchable strain sensors are still facing limitations that are yet to be resolved.
A KAIST research team led by Professor Inkyu Park from the Department of Mechanical Engineering suggested that an optical-type stretchable strain sensor can be a good alternative to resolve the limitations of conventional piezo-resistive and piezo-capacitive strain sensors, because they have high stability and are less affected by environmental disturbances. The team then introduced an optical wearable strain sensor based on the light transmittance changes of a CNT-embedded elastomer, which further addresses the low sensitivity problem of conventional optical stretchable strain sensors.
In order to achieve a large dynamic range for the sensor, Professor Park and his researchers chose Ecoflex as an elastomeric substrate with good mechanical durability, flexibility, and attachability on human skin, and the new optical wearable strain sensor developed by the research group actually shows a wide dynamic range of 0 to 400%.
In addition, the researchers propagated the microcracks under tensile strain within the film of multi-walled CNTs embedded in the Ecoflex substrate, changing the optical transmittance of the film. By doing so, it was possible for them to develop a wearable strain sensor having a sensitivity 10 times higher than conventional optical stretchable strain sensors.
The proposed sensor has also passed the durability test with excellent results. The sensor’s response after 13,000 sets of cyclic loading was stable without any noticeable drift. This suggests that the sensor response can be used without degradation, even if the sensor is repeatedly used for a long time and in various environmental conditions.
Using the developed sensor, the research team could measure the finger bending motion and used it for robot control. They also developed a three-axes sensor array for body posture monitoring. The sensor was able to monitor human motions with small strains such as a pulse near the carotid artery and muscle movement around the mouth during pronunciation.
Professor Park said, “In this study, our group developed a new wearable strain sensor platform that overcomes many limitations of previously developed resistive, capacitive, and optical-type stretchable strain sensors. Our sensor could be widely used in a variety of fields including soft robotics, wearable electronics, electronic skin, healthcare, and even entertainment.”
This work was supported by the National Research Foundation (NRF) of Korea.
Publication:
Jimin Gu, Donguk Kwon, Junseong Ahn, and Inkyu Park. (2020) “Wearable Strain sensors Using Light Transmittance Change of Carbon Nanotube-Embedded Elastomers with Microcracks” ACS Applied Materials & Interfaces. Volume 12. Issue 9. Available online at https://doi.org/10.1021/acsami.9b18069
Profile:
Inkyu Park
Professor
inkyu@kaist.ac.kr
http://mintlab1.kaist.ac.kr
Micro/Nano Transducers Laboratory (MINT Lab)
Department of Mechanical Engineering (ME)Korea Advanced Institute of Science and Technology (KAIST)
Profile:
Jimin Gu
Ph.D. Candidate
mint9411@kaist.ac.kr
http://mintlab1.kaist.ac.kr
MINT Lab
KAIST ME
(END)
2020.03.20 View 15586 -
Bioengineers develop a new strategy for accurate prediction of cellular metabolic fluxes
A team of pioneering South Korean scientists has developed a new strategy for accurately predicting cellular metabolic fluxes under various genotypic and environmental conditions. This groundbreaking research is published in the journal Proceedings of the National Academy of Sciences of the USA (PNAS) on August 2, 2010.
To understand cellular metabolism and predict its metabolic capability at systems-level, systems biological analysis by modeling and simulation of metabolic network plays an important role. The team from the Korea Advanced Institute of Science and Technology (KAIST), led by Distinguished Professor Sang Yup Lee, focused their research on the development of a new strategy for more accurate prediction of cellular metabolism.
“For strain improvement, biologists have made every effort to understand the global picture of biological systems and investigate the changes of all metabolic fluxes of the system under changing genotypic and environmental conditions,” said Lee. The accumulation of omics data, including genome, transcriptome, proteome, metabolome, and fluxome, provides an opportunity to understand the cellular physiology and metabolic characteristics at systems-level. With the availability of the fully annotated genome sequence, the genome-scale in silico (means “performed on computer or via computer simulation.”) metabolic models for a number of organisms have been successfully developed to improve our understanding on these biological systems. With these advances, the development of new simulation methods to analyze and integrate systematically large amounts of biological data and predict cellular metabolic capability for systems biological analysis is important.
Information used to reconstruct the genome-scale in silico cell is not yet complete, which can make the simulation results different from the physiological performances of the real cell. Thus, additional information and procedures, such as providing additional constraints (constraint: a term to exclude incorrect metabolic fluxes by restricting the solution space of in silico cell) to the model, are often incorporated to improve the accuracy of the in silico cell.
By employing information generated from the genome sequence and annotation, the KAIST team developed a new set of constraints, called Grouping Reaction (GR) constraints, to accurately predict metabolic fluxes. Based on the genomic information, functionally related reactions were organized into different groups. These groups were considered for the generation of GR constraints, as condition- and objective function- independent constraints. Since the method developed in this study does not require complex information but only the genome sequence and annotation, this strategy can be applied to any organism with a completely annotated genome sequence.
“As we become increasingly concerned with environmental problems and the limits of fossil resources, bio-based production of chemicals from renewable biomass has been receiving great attention. Systems biological analysis by modeling and simulation of biological systems, to understand cellular metabolism and identify the targets for the strain improvement, has provided a new paradigm for developing successful bioprocesses,” concluded Lee. This new strategy for predicting cellular metabolism is expected to contribute to more accurate determination of cellular metabolic characteristics, and consequently to the development of metabolic engineering strategies for the efficient production of important industrial products and identification of new drug targets in pathogens.”
2010.08.05 View 12290 -
KAIST Professors Article Featured as Cover Thesis of Biotechnology Journal
An article authored by a research team of Prof. Sang-yup Lee at the Department of Chemical and Biomolecular Engineering and Dr. Jin-Hwan Park at the KAIST Institute for the BioCentury has been featured as the cover thesis of the August 2008 issue of Trends in Biotechnology.
The paper, titled "General strategy for strain improvement by means of systems metabolic engineering," focuses on the application of systems biology for the development of strains and illustrates future prospects. Trends in Biotechnology, published by Cell Press, is one of the most prestigious review journals in the field.
Jin-Hwan Park, the primary author of the research thesis, said that the KAIST team"s research work was expected to provide substantial help to researchers involved in biotechnology industry.
The strategy has been established on the basis of the experiences gained in the actual microbial production process using the systems biology methods which his research team has recently worked on, Prof. Park said.
2008.07.24 View 13808 -
KAIST, GS Caltex Jointly Develop New Bacteria to Produce Biobutanol
KAIST and GS Caltex, Korea"s second-largest refiner, have jointly developed a new strain of bacteria to produce biobutanol, which is regarded as a promising next-generation biofuel, KAIST authorities said on Monday (June 2).
A research team led by Prof. Sang-Yup Lee of the Chemical and Biomolecular Engineering Department and researchers of GS Caltex succeeded in developing an improved strain of bacteria which enables to produce a large amount of biobutanol in the process of fermenting biomass. The research team has applied for international patent for the new technology.
Biomass refers to living and recently dead biological material that can be used as fuel or for industrial production. It usually refers to plant matter grown for use as biofuel, but it also includes plant or animal matter used for production of fibers, chemicals or heat.
In the 1970s and 1980s when scientists began researching the possibilities of alternative fuels, bacteria were used in the process of fermenting biomass. This ABE (acetone, butanol, ethanol) fermentation process yields butanol, acetone, and ethanol in a ratio of 6:3:1, respectively. Acetone produced in this process is not usable.
The newly developed technology to produce biobutanol has an advantage of lowering production cost by eliminating the process to separate acetone from butanol. This has been made possible by improving the bacteria used for the fermentation in metabolic engineering terms, and producing butanol and ethanol only in a ratio of 6:1, while curbing the generation of acetone.
In comparison with bioethanol, also a biofuel mixture which is currently under widespread use in some countries, butanol is more easily transported with gasoline and diesel through pipelines because of its lower tendency to separate from the fuel when contaminated with water. Butanol is also less corrosive than ethanol, another reason its transport through pipeline is preferable.
Global interest in full utilization of biomass and development of other alternative energy including biobutanol has deepened in recent years, as crude oil prices have skyrocketed to record levels and climate changes resulting from the excessive use of fossil fuel have been causing various problems around the world.
2008.06.04 View 11710