Title: Construction of cell factories for efficient production of aromatic compounds Astract: The massive consumption of fossil resources and the rapid development of the chemical industry have greatly advanced human civilization; however, they have also led to challenges such as resource unsustainability and environmental pollution. Bio-manufacturing of aromatic chemicals offers a promising solution for achieving sustainable development, in which the construction of efficient artificial cell factories plays a central role and is expected to significantly promote the growth of the bioeconomy. This report outlines the current scientific and technological challenges in cell factory construction and discusses emerging technologies and strategies for developing efficient cell factories. Specifically, it highlights advances in exploring novel enzyme functions, discovering new biochemical reactions, designing and constructing non-natural metabolic pathways, creating metabolic driving forces, establishing stable self-regulating microbial co-culture systems, and dynamically regulating metabolic flux through quorum sensing. Using the biosynthesis of aromatic esters and the industrial production of arbutin as representative examples, this report provides insights into the green manufacturing of aromatic chemicals and demonstrates the vast potential of synthetic biology. Personal Profile: Qipeng Yuan is a Distinguished Professor of Changjiang Scholar and deputy director of the State Key Laboratory of Chemical Resource Engineering. His research areas include synthetic biology and metabolic engineering, large-scale high-purity preparation and activity research of natural products. He has published more than 300 articles. He has more than 60 authorized Chinese invention and PCT patents, several of which has been implemented for industrial production, creating good economic benefits. He has got the National Science and Technology Progress Award, the 11th China Youth Science and Technology Award, and 5 provincial and ministerial level awards. He is the member of several scientific committees such as Chinese Society of Industrial Biochemistry and Molecular Biology.

Title: DiPaSE: A one-pot DNA assembly method for accurate and efficient refactoring of high-GC, long BGCs Astract: Actinobacteria constitute a rich source of bioactive natural products (NPs). However, the engineering of their long, high-GC biosynthetic gene clusters (BGCs) remains challenging owing to the low efficiency of conventional multiplex editing methods. To address this limitation, a novel one-pot DNA assembly method termed “DiPaSE” (direct pathway synthesis and editing) has been developed for the efficient synthesis and simultaneous editing of high-GC BGCs. DiPaSE enables the accurate assembly of multiple high-GC DNA fragments with a size of up to 60 kb, allowing seamless insertions and deletions without sacrificing assembly efficiency. With this method, researchers have successfully characterized cryptic genes within the aureothin BGC and achieved a substantial improvement in its natural product titer. By relying on standard PCR, type IIP restriction enzymes, and E. coli, this workflow offers a simple, cost-effective, and versatile platform for genome mining, BGC refactoring, and the rational design of artificial biosynthetic pathways, thereby facilitating advances in synthetic biology applications. Personal Profile: Dr. Satoshi Yuzawa currently works as a Project Assistant Professor at the Institute for Advanced Biosciences at Keio University (Japan). He is interested in high-GC, long biosynthetic gene cluster engineering, which underlies the production of natural and unnatural compounds with potential applications in drugs and fuels. In particular, he aims to understand and manipulate these complex genetic systems to advance metabolic engineering and synthetic biology. For this, his group combines cutting-edge genetic engineering techniques with diverse research backgrounds gained through his previous positions in the US, including the University of California, Berkeley. An active contributor to the field, he has published over 30 scientific papers and was awarded the Hamada Award from the Society for Actinomycetes Japan in 2021.

Title: De novo design of functional protein complexes using deep generative models Astract: Protein complexes such as protein oligomers, cages, bundles, and patterned layers exist widely in nature and can also be constructed artificially. They participate in a variety of biological processes, including genetic material delivery, immune activation, and disease pathogenesis. Therefore, the design of artificial protein nanostructures that can regulate these biological processes has attracted extensive research attention.Over the past few decades, computational protein design has mainly relied on physics-based methods, such as scoring functions derived from theoretical chemistry and physics. However, recent advances in AI-based methods, including protein structure prediction, sequence design, and generative models, have greatly broadened the scope of achievable protein structure design.In this talk, he will provide an overview of the computational design of de novo protein nanostructures using AI-based software and present several examples of designed nanostructures, such as virus-like nanocages. Experimentally, the designed proteins were expressed in Escherichia coli, and the assembled nanostructures were verified using electron microscopy. Personal Profile: Dr. Sangmin Lee is an Assistant Professor in the Department of Chemical Engineering at Pohang University of Science and Technology (POSTECH), South Korea. His research focuses on de novo protein design, protein nanostructures, and the self-assembly and phase behavior of bio-inspired nanomaterials. Before joining POSTECH, he was a postdoctoral scholar with Prof. David Baker at the Howard Hughes Medical Institute and the University of Washington. He received his Ph.D. in Chemical Engineering from the University of Michigan under the supervision of Prof. Sharon Glotzer. His work has been published in leading journals including Nature, Nature Materials, Nature Chemistry, PNAS, and Science Advances.

Title: Hierarchical Approaches to construct High-efficient Microbial Production Hosts Overcoming Endogenous Metabolic Limitations Astract: Metabolic engineering leverages native pathways and enzymes to enable microbial bioproduction; however, sub-optimal enzymatic activities and endogenous metabolic constraints often limit production efficiency and yield. Because microorganisms have evolved to prioritize survival rather than chemical synthesis, improving bioproduction typically requires multi-scale engineering strategies spanning both pathway- and enzyme-level interventions using two different engineering approaches: rational engineering and evolutionary engineering. In the enzymatic reaction scale, the researchers engineered several enzymes which showed improved catalytic activities or novel reactions to redirect more flux toward the target chemical production. In the metabolic pathway scale, more metabolic fluxes derived from substrates were rewired toward the target chemical by balancing them at the major metabolic node or redesigning the pathways to avoid carbon loss steps. Together, these results illustrate how coordinated pathway rewiring and enzyme engineering can effectively overcome native metabolic constraints, providing a generalizable framework for maximizing carbon efficiency and advancing sustainable bioproduction of value-added chemicals. Personal Profile: Dr. Dae-yeol Ye currently works as an assistant professor for biochemical engineering at Gachon University (South Korea). He is interested in the development of high-efficient microbial cell factories which overcome their endogenous metabolic limitations. Especially, he is trying to redirect more resources derived from carbon sources into value-added target chemicals, consequently leading to enhanced production results. He aims to understand central carbon metabolism involved in major energy metabolism and supply of intermediates for chemical production. Also, he is also trying to utilize regulatory factors as sensory elements to develop genetically encoded biosensors, subsequently targeted for evolutionary enzyme engineering. Based on these, he is trying to develop construction of a novel metabolic pathway by biosensor-mediated enzyme engineering and metabolic flux optimization.

Title: Unlocking the full genetic potential of Streptomyces for next level of biomolecular engineering Astract: Streptomyces, soil-dwelling gram-positive bacteria, remain promising microorganisms for natural product production, known as secondary metabolites (SMs), with diverse pharmaceutical bioactivities such as antimicrobial, antifungal, anticancer, and immunosuppressive properties. Despite Streptomyces species harboring over 30 SM biosynthetic gene clusters (smBGCs), there is a lack of linkage between these clusters and their respective products, with the majority remaining silent under laboratory conditions, thereby limiting their effective utilization. To fully harness Streptomyces' genomic potential, the researcher has employed systems and synthetic biology approaches for: (1) Mining novel smBGCs; (2) Understanding the regulation of smBGCs to awaken them; (3) Enhancing SM production rationally based on multi-omics data-driven bottleneck determination; and (4) Reprogramming SM biosynthetic machinery for retrobiosynthesis. Systems biology approach offers a comprehensive understanding of secondary metabolism and potential engineering targets, while synthetic biology and retrobiosynthesis approach enable the production of new-to-nature compounds, overcoming conventional metabolic engineering challenges. Personal Profile: Prof. Namil Lee joined the Graduate School of Engineering Biology at KAIST, Korea, as an Assistant Professor in September 2025. Before joining KAIST, he was a postdoctoral researcher in the laboratory of Prof. Jay D. Keasling at the University of California, Berkeley, and the Joint BioEnergy Institute (JBEI). He earned his Ph.D. from KAIST. Prof. Lee’s research integrates systems and synthetic biology to unlock the full genetic potential of microbial hosts. His work focuses on understanding and engineering secondary metabolism, particularly through the reprogramming of natural product biosynthetic machinery to generate new-to-nature molecules.

Title: Toward Digital Cells and Humans Astract: Mechanistic metabolic models provide a structured framework for linking genotype to phenotype through cellular metabolism. Researchers developed genome-scale models for S. cerevisiae (e.g., Yeast8) and extended them to include additional biological processes and constraints, enabling quantitative simulation of metabolic states. To enhance model scope and predictive accuracy, they integrated deep learning methods (e.g., DLKcat for enzyme kinetics prediction). These advances improve phenotype prediction and support synthetic biology applications. At the whole-body level, they constructed Human2—a dynamic, multi-organ metabolic model capable of simulating inter-organ metabolism and dietary responses across over 18,000 food components. Collectively, these efforts establish a unified, scalable framework bridging cellular mechanisms and systemic human physiology, laying the groundwork for digital cells and digital human twins in systems biology and precision medicine. Personal Profile: Dr. Feiran Li is an Assistant Professor at Tsinghua University’s Shenzhen International Graduate School (SIGS), specializing in constraint-based modeling, machine learning, and synthetic biology. She received her Ph.D. from Chalmers University of Technology in Sweden in 2021 under the supervision of Prof. Jens Nielsen and continued her research in the Nielsen Lab as a postdoc until 2023. During her Ph.D. and postdoctoral training, Dr. Li published first-author papers in leading journals such as Nature Catalysis, Nature Communications, PNAS, Nucleic Acids Research, and Molecular Systems Biology. She has been recognized with honors such as the National Overseas High-level Talents (Youth) Project, MIT Technology Review’s TR35 (China), and AI100 Youth Pioneer. Her research focuses on developing advanced computational models to investigate metabolic systems and applying them to address key challenges in biotechnology and biomedicine.

Title: The use of Aquatic Vaccines and Therapeutics in Aquaculture Astract: Aquatic vaccines and therapeutics are fundamental to sustainable aquaculture, addressing the increasing incidence of infectious diseases associated with farming intensification, global animal movement, and environmental stressors. Conventional reliance on antibiotics has contributed to antimicrobial resistance, environmental pollution, and food safety risks, highlighting the need for preventive health-based strategies. This talk highlights an integrated disease management approach that combines biosecurity, comprehensive husbandry practices, probiotics, immunostimulants, bacteriophages, medicinal plants, and vaccination. Particular emphasis is placed on vaccines, especially feed-based oral vaccines, as effective, eco-friendly tools that stimulate both mucosal and systemic immune responses while reducing handling stress. Collectively, these approaches highlight the critical role of vaccines and alternative therapeutics in strengthening the resilience and long-term sustainability of aquaculture production systems. Personal Profile: Dr. Aslah Mohamad is a Lecturer at the China-ASEAN College of Marine Sciences, Xiamen University Malaysia. He specializes in vaccinology and aquaculture biotechnology, with a research focus on fish health management, aquatic animal vaccine development, and sustainable aquaculture systems. His work emphasizes understanding the mechanisms and efficacy of fish vaccines, including feed-based multivalent vaccines, as well as the development of aquatic animal therapeutics to mitigate antimicrobial resistance (AMR) in aquaculture. In addition, Dr. Aslah’s research explores the application of microalgae-derived products in aquafeeds as functional health management tools, contributing to environmentally responsible and resilient aquaculture practices.

Title: Enzyme Specificity Unlocked : The EZSCAN Advantage Astract: Identifying amino acid residues critical for determining substrate and cofactor specificity is essential for understanding enzyme mechanisms and guiding protein engineering. Current methods struggle to distinguish these residues from those merely maintaining structural stability. The research team developed a computational approach to identify residues influencing specificity among structurally homologous enzymes by framing sequence comparison as a classification problem—an innovation that enabled the objective identification of key functional differences. This method was validated using four pairs of enzymes and accurately predicted known specificity-determining residues. Experimental validation further demonstrated that introducing the predicted key substitutions could successfully alter substrate and cofactor specificity while preserving protein expression levels, highlighting the method’s robust effectiveness. The team has since implemented this approach as a practical web tool, EZSCAN (Enzyme Substrate-specificity and Conservation Analysis Navigator), designed for the rapid identification of functionally critical amino acid residues in enzymes. Personal Profile: Dr. Niide has been serving as an Assistant Professor at the Graduate School of Information Science and Technology, University of Osaka, Japan, since 2020. He earned his Ph.D. in Applied Chemistry from Kyushu University. Before joining the University of Osaka, he received extensive training in high- throughput screening in Umetsu Laboratory at Tohoku University and in computational protein design in the Kuhlman Laboratory at the University of North Carolina at Chapel Hill, where both he deepened his understanding of enzyme structure–function relationships through advanced protein engineering. His current research focuses on integrating protein engineering with metabolic engineering to rationally design enzymes that enhance or alter cellular functions. In particular, his work has contributed to elucidating how amino acid conservation, structural dynamics, and machine learning–based models can be combined to predict and understand protein function.

Title: Programming Gut Microbial Metabolism through Synthetic Biology for Intestinal Health Astract: The human gut microbiota constitutes a complex ecosystem critical for host homeostasis, and its disruption is associated with various intestinal diseases. A key area of Dr. Lee’s research is microbial bile acid metabolism: primary bile acids assist in fat digestion, while gut microbes transform a portion into secondary bile acids that can drive intestinal inflammation, epithelial damage, and colorectal tumorigenesis. This presentation will highlight how synthetic biology strategies can be used to reprogram gut microbial metabolism, attenuate tumor-promoting signals, and restore intestinal balance. By uncovering mechanistic principles of microbiome–host interactions and engineering targeted microbial therapeutics, his work provides new approaches for preventing and treating intestine-related disorders driven by dysregulated bile acid metabolism. Personal Profile: Dr. Jae Won Lee is an Assistant Professor of Biotechnology at Sungshin Women’s University, South Korea. His research centers on synthetic biology for sustainability and human health. During his doctoral studies, he engineered model organisms including Saccharomyces cerevisiae and Escherichia coli for the biosynthesis of high-value biochemicals, such as 2,3-butanediol, fucose, and fucosylated human milk oligosaccharides with prebiotic functions. Since joining Sungshin Women’s University, his work has shifted to developing engineered microorganisms as living therapeutics, with a focus on understanding microbiome–host interactions and reprogramming gut microbial metabolism to maintain intestinal homeostasis.

Title: From Empirical Tuning to Platform Design: CRISPR Screening–Enabled Mammalian Cell Engineering Astract: The expanding diversity of complex biotherapeutics (e.g., bispecific antibodies, hard-to-express proteins) exposes inherent limitations of empirically optimized mammalian cell factories. While CHO cell-based monoclonal antibody production is mature, next-generation biologic manufacturing is hindered by poorly characterized modality-specific bottlenecks. Leveraging advances in mammalian synthetic biology and genome editing, genome-wide CRISPR screening has become an unbiased tool for systematic cell engineering. This presentation introduces a virus-free, RMCE-based CRISPR screening platform for scalable knockout/activation screens in CHO cells; integrating productivity-, stress- and FACS-based selection, the platform identifies novel genetic and epigenetic targets regulating cell fitness, stress tolerance and transgene expression. Combining CRISPR-driven target discovery with precise knock-in gene expression control provides a rational framework for platform-level mammalian cell factory design, shifting cell engineering from empirical tuning to predictive, modality-adaptive platforms for next-generation biotherapeutics manufacturing. Personal Profile: Dr. Jae Seong Lee is an Associate Professor at the Graduate School of Engineering Biology, KAIST, Korea. He earned his B.S. and Ph.D. from KAIST and completed postdoctoral research at the Technical University of Denmark, where he served as a founding member of the CHO Cell Line Engineering and Design section at the Novo Nordisk Foundation Center for Biosustainability. There, he developed key CRISPR/Cas9-based genome engineering technologies for CHO cell factories, now widely used in mammalian bioprocessing for therapeutic protein production. After returning to Korea in 2017, he joined Ajou University as an Assistant Professor before moving to KAIST. His current research focuses on developing a mammalian synthetic biology toolkit, integrating genome-wide screening, tunable gene expression systems, and AI-driven approaches for advanced cell line engineering and biomanufacturing.

Title: Development of nucleic acid-based gene regulators for metabolic engineering and molecular diagnosis Astract: Synthetic biology aims at providing solutions for the challenges of modern society and paving new ways to understand life. Realizing the true potential of synthetic biology is dependent on the ability to regulate gene expression. Nucleic acids offer new opportunities for developing artificial gene regulators based on their programmability, versatility, low genetic footprint, and economic production both in vivo or in vitro. In this talk, the speaker will introduce examples of artificial gene regulators developed through rational design and artificial evolution. Specifically, an efficient development process for RNA-based inducible gene regulators and their application to sensing of small molecules will be presented. Additionally, a rationally-designed nucleic acid-based molecular program for rapid diagnosis of pathogens called SENSR will be discussed. Personal Profile: Dr. Sungho Jang currently serves as an Associate Professor in the Division of Bioengineering at Incheon National University, South Korea. His research is centered on redesigning biological systems by integrating principles from synthetic biology and artificial evolution. A core focus of his approach is the development and application of nucleic acid-based tools, particularly synthetic RNA devices like riboswitches, to serve as artificial gene regulators and metabolite sensors. This expertise is applied to develop advanced platforms for the production of valuable chemicals and pharmaceuticals, the manipulation of the microbiome for therapeutic purposes, and the creation of novel tools for the molecular diagnosis of diseases.

Title: Development of Engineered Living Biotherapeutic Products (eLBPs) through Systems and Synthetic Biology for Enhanced Metabolic Activities in the Gut Astract: The convergence of systems biology and synthetic biology provides a powerful framework for the development of engineered living biotherapeutic products (eLBPs) with improved functionality and metabolic performance in the gut. This study presents a systems-level strategy for designing synthetic microbial therapeutics capable of sustaining high metabolic activities under intestinal conditions. Using Saccharomyces boulardii and Escherichia coli Nissle 1917 as chassis organisms, the researchers integrated multi-omics data with genome-scale metabolic modeling to identify and overcome key bottlenecks limiting microbial metabolism and recombinant protein secretion in the gut. Specifically, S. boulardii strains engineered to metabolize host-derived sugars such as L-fucose and lactose demonstrated enhanced metabolic activity through continuous carbon supply, while E. coli Nissle exhibited improved energy efficiency by eliminating trehalose metabolism–related constraints under anaerobic conditions. These findings establish a rational design framework for constructing eLBPs with enhanced intestinal metabolic activity, bridging computational modeling with synthetic biology to achieve robust and predictable function within complex gut ecosystems. Personal Profile: Dr. Jungyeon Kim is an Assistant Professor in the Department of Bioindustrial Sciences at Seoul National University (Graduate School of International Agricultural Technology, Republic of Korea). His research focuses on understanding and engineering microbial systems through integrative systems biology and synthetic biology approaches. His group applies multi-omics analysis, genome-scale metabolic modeling, and CRISPR-based genome engineering to design microbial platforms with enhanced metabolic and functional traits. In particular, his work aims to elucidate regulatory networks governing microbial metabolism and translate this knowledge into the rational design of next-generation probiotics and microbial cell factories.

Title: Exploring the Potential of Biocatalysis for Abiotic Chemical Transformations Astract: With the rapid advancement of biotechnology, biocatalysis has emerged as a promising and sustainable approach for the synthesis of valuable chemicals. A major challenge associated with biocatalysis is to expand the catalytic repertoire of enzymes to meet the requirements of synthetic chemistry. In this context, the researcher’s group is working toward the discovery of novel enzymes capable of catalyzing abiotic chemical transformation by leveraging principles of organic chemistry. In this presentation, they will introduce their recent progress in identifying novel bacterial enzymes capable of catalyzing the NHC-mediated radical acylation and other abiotic chemical transformations. Personal Profile: Dr. Shunsuke Kato received his Ph.D. in Applied Chemistry from Osaka University, Graduate School of Engineering, in 2021 under the supervision of Prof. Takashi Hayashi. During his doctoral studies, he joined the group of Prof. Kazushi Mashima (Graduate School of Engineering Science, Osaka University) in 2016. From 2017 to 2018, he conducted research as a visiting scholar in the group of Prof. Ulrich Schwaneberg at the Institute of Biotechnology, RWTH Aachen University. In 2019, he undertook an internship at Sumitomo Chemical Co., Ltd. (Bioscience Research Laboratory). In 2021, he was promoted to Assistant Professor in the Department of Applied Chemistry, Graduate School of Engineering, Osaka University. In 2025, he was appointed Associate Professor at Engineering Biology Research Center, Kobe University. His current research interests lie in the area of biocatalysis, including the genome mining of novel enzymes, and their application to the metabolic engineering.

Title: Metabolic engineering of Escherichia coli for de novo production of lauryl glucoside Astract: Lauryl glucoside is a biodegradable, non-ionic surfactant commonly used in cosmetics, yet its conventional chemical synthesis raises sustainability concerns. To address this, the researchers engineered Escherichia coli BL21(DE3) with a novel pathway for microbial lauryl glucoside production. They first optimised the biosynthesis of the precursor 1-dodecanol, then screened a panel of UDP-glycosyltransferases for their ability to convert it into lauryl glucoside. Among six candidates, MtH2 from Medicago truncatula demonstrated the highest activity, and its product formation was confirmed by HPLC and targeted LC-MS. Pathway analysis revealed that limited 1-dodecanol supply was the key bottleneck, and supplementation experiments substantially improved lauryl glucoside yields. Overall, this work establishes a proof of concept for sustainable microbial production of lauryl glucoside and provides new insight into pathway bottlenecks for future optimisation. Personal Profile: Dr. Pachara Sattayawat is an Assistant Professor in Microbiology at the Department of Biology, Faculty of Science, Chiang Mai University. She received her PhD in microbial metabolic engineering and synthetic biology from Imperial College London, UK. Her research focuses on engineering bacteria for enhanced characteristics, particularly for the bioproduction of high-value chemicals and recombinant proteins. Her work spans system and pathway design, protein discovery, enzyme characterisation, and implementation in microbial hosts using synthetic biology approaches. More recently, her interests have expanded to engineering Escherichia coli for therapeutic antibody production in cancer research, as well as developing engineered symbionts for chemical detoxification.

Title: Tackling the global spread of AMR using genome-resolved metagenomics and AI Astract: We live in a microbial world (≈1 million species), but humanity’s adversarial microbial relationship comes from a few pathogens and widespread antimicrobials. Microbe eradication often fails—disinfected areas recolonize fast, and antibiotics fuel resistant pathogens. Global antimicrobial resistance (AMR) in common pathogens (e.g., ESKAPE) threatens healthcare; as effective antibiotics shrink, some pathogens may become untreatable, endangering millions of hospital patients. AMR already causes >1 million annual deaths, with the UN projecting it will surpass all cancers (>10 million/year) by 2050. New methods are needed to track AMR transmission and use ecology to reduce AMR reservoirs. Long-read sequencing-aided genome-resolved metagenomics can transform microbial surveillance, as seen in hospital and gut pathogen tracking. To understand microbial community assembly and pathogen resistance, new AI/modelling tools (using high-throughput metagenomic data) provide mechanistic insights. Combined with data mining, these help study microbiome recovery from antibiotics and develop new biotherapeutics to stop AMR pathogen spread. Personal Profile: Prof. Niranjan Nagarajan is currently an Associate Professor at the National University of Singapore’s School of Medicine and Department of Computer Science, and Associate Director & Senior Group Leader at ASTAR’s Genome Institute of Singapore. He holds a 2000 B.A. in Computer Science and Mathematics (Ohio Wesleyan University), a master’s in Computer Science (Cornell University), and a 2006 Ph.D. in Computer Science (Cornell University, Advisor: Prof. Uri Keich). After postdoctoral research on genome assembly and metagenomics at the University of Maryland (Advisor: Prof. Mihai Pop), he joined ASTAR as a Principal Investigator in 2009. His lab focuses on advanced genome analytic tools for microbial community function and human health impact, pioneering genome-resolved metagenomics assembly tools, studying microbiomes in antimicrobial resistance (AMR) transmission and Asian skin conditions via systems biology. He has over 100 papers (>20,000 citations, H-index 64), is a 2021-2023 Highly Cited Researcher, and won the 2024 National Research Foundation Investigatorship (Singapore).