Article
Biotechnology & Applied Microbiology
Gahyeon Ryu, Gi Bae Kim, Taeho Yu, Sang Yup Lee
Summary: The establishment of a bio-based circular economy is crucial for addressing the climate crisis and promoting sustainable development. Designing metabolic pathways for microbial cell factories is essential, and computer-supported tools and deep learning techniques can aid in pathway prediction and enzyme discovery. Leveraging these computational tools and strategies, particularly the capabilities of deep learning, has the potential to accelerate the advent of a bio-based circular economy.
METABOLIC ENGINEERING
(2023)
Article
Biochemical Research Methods
Christopher J. Hartline, Fuzhong Zhang
Summary: Metabolite biosensors based on metabolite-responsive transcription factors are important components in synthetic biology for sensing and controlling cellular metabolism. This study investigates the impact of growth rate on biosensor performance and reveals that different biosensors exhibit different growth rate dependencies in their dynamic range. The study also develops a kinetic model to explore the effects of tuning biosensor parameters on dynamic range and its growth rate dependence.
ACS SYNTHETIC BIOLOGY
(2022)
Review
Chemistry, Analytical
Jianli Zhang, Xinyu Gong, Qi Gan, Yajun Yan
Summary: Plant natural products (PNPs) have enormous potential in global markets, and microbial cell factories (MCFs) offer an economical and sustainable alternative for their synthesis. However, heterologous synthetic pathways often lack native regulatory systems, leading to challenges in PNPs production. To overcome these challenges, biosensors responsive to PNPs and their precursors have been developed and engineered as powerful tools for artificial regulatory networks.
Review
Biochemistry & Molecular Biology
Yang Cheng, Xinyu Bi, Yameng Xu, Yanfeng Liu, Jianghua Li, Guocheng Du, Xueqin Lv, Long Liu
Summary: Optimizing metabolic pathways in microbial cell factories is crucial for efficient biotechnological production processes. Machine learning has been used to build data-driven models and accelerate development in areas such as genetic engineering and pathway optimization. This review discusses recent applications of machine learning in genome-scale metabolic model construction, enzyme engineering, and gene regulatory element design, as well as the limitations and potential solutions to these methods.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Biotechnology & Applied Microbiology
Christopher J. Hartline, Alexander C. Schmitz, Yichao Han, Fuzhong Zhang
Summary: Metabolic engineering enables the production of valuable chemicals using microbial organisms, with dynamic metabolic engineering allowing cells to autonomously adjust flux in response to their metabolic state. The review discusses theoretical works, molecular mechanisms, and applications of dynamic control systems in improving metrics in metabolic engineering.
METABOLIC ENGINEERING
(2021)
Review
Biochemical Research Methods
Woo Dae Jang, Gi Bae Kim, Yeji Kim, Sang Yup Lee
Summary: This paper reviews recent studies on AI-aided protein engineering and design, focusing on directed evolution that uses AI approaches to efficiently construct mutant libraries. Additionally, recent works on AI-aided pathway design strategies, including template-based and template-free approaches, are discussed.
CURRENT OPINION IN BIOTECHNOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Dongdong Zhao, Xinna Zhu, Hang Zhou, Naxin Sun, Ting Wang, Changhao Bi, Xueli Zhang
Summary: Effective metabolic pathways are crucial for efficient cell factories, and utilizing CRISPR technology in pathway engineering can enhance efficiency, reduce costs, and simplify target customization. This technology has been proven to be robust and effective in various organisms.
METABOLIC ENGINEERING
(2021)
Article
Biotechnology & Applied Microbiology
Yuan Zhu, Ying Li, Ya Xu, Jian Zhang, Linlin Ma, Qingsheng Qi, Qian Wang
Summary: The study focused on designing a bifunctional glycolysis flux biosensor to dynamically regulate glycolysis flux for enhanced production of desired biochemicals in microbial cell factories. These engineered biosensors effectively balanced metabolic flux imbalance and improved the yield of target products in biosynthesis processes.
METABOLIC ENGINEERING
(2021)
Article
Biotechnology & Applied Microbiology
Xiaoyu Yang, Jianhui Liu, Jin Zhang, Yu Shen, Qingsheng Qi, Xiaoming Bao, Jin Hou
Summary: In this study, a quorum sensing-regulated protein degradation circuit was designed for dynamic metabolic pathway control in Saccharomyces cerevisiae. Utilizing quorum sensing circuits to regulate auxin synthesis led to an 80% increase in ?-farnesene production. This population-regulated protein degradation system extends dynamic regulation to the protein level and offers a promising approach for metabolic pathway control.
METABOLIC ENGINEERING
(2021)
Article
Chemistry, Applied
Miaomiao Hu, Mengli Li, Chenchen Li, Tao Zhang
Summary: In this study, an efficient engineered strain for the biosynthesis of LNFP I was reported by rational design of metabolic pathways in Escherichia coli. The engineered strains produced high yields of LNFP I in fed-batch cultivation, with a conversion rate of lacto-N-tetraose to LNFP I reaching the highest level reported so far. The LNFP I-produced platform established here is broadly suitable for the production of complex and branched oligosaccharides.
CARBOHYDRATE POLYMERS
(2022)
Article
Biotechnology & Applied Microbiology
Szu-Yi Hsu, Jihaeng Lee, Adam Sychla, Michael J. Smanski
Summary: Modern tools in DNA synthesis and assembly provide genetic engineers with precise control over the design of complex gene systems. However, there is a lack of systematic approaches to optimize the performance of genetic constructs. This study explores the use of a Plackett-Burman design to improve the production of a specific compound in Streptomyces.
METABOLIC ENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Valentina Goldfinger, Marius Spohn, Jens-Peter Rodler, Melanie Sigle, Andreas Kulik, Max J. Cryle, Johanna Rapp, Hannes Link, Wolfgang Wohlleben, Evi Stegmann
Summary: The control of precursor delivery is crucial for the assembly of glycopeptide antibiotics (GPA). The cross-regulation between the tyrosine and phenylalanine pathways plays an important role in GPA production. Overexpression of the key enzyme gene involved in the tyrosine pathway significantly increased antibiotic yield, while overexpression of the key enzyme gene in the phenylalanine pathway had no positive effects.
METABOLIC ENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Ryutaro Kawai, Yoshihiro Toya, Hiroshi Shimizu
Summary: Combining growth-associated pathway engineering based on FBA and ALE is an effective method to increase the production of useful compounds. This study introduces a novel ALE approach based on mutualistic co-culture, which significantly improves the yield of phenylalanine production.
BIOPROCESS AND BIOSYSTEMS ENGINEERING
(2022)
Article
Biotechnology & Applied Microbiology
Chong-Yang Ren, Yong Liu, Wen-Ping Wei, Junbiao Dai, Bang-Ce Ye
Summary: This study created a valuable heterologous host Ab Delta ery by knocking out the erythromycin biosynthesis gene cluster, which showed higher production of heterologous products than the wild type strain.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Chang-ye Hui, Shun-yu Hu, Li-mei Li, Jian-pei Yun, Yan-fang Zhang, Juan Yi, Nai-xing Zhang, Yan Guo
Summary: This study demonstrates the successful production of Hg(II)-responsive biosensors using metabolically engineered E. coli. By reconstructing the carotenoid synthetic pathway, the engineered E. coli produces red and orange biosensors that can qualitatively and quantitatively detect the ecotoxicity of Hg(II).
Article
Chemistry, Multidisciplinary
Jingyao Li, Yaguang Zhu, Han Yu, Bin Dai, Young-Shin Jun, Fuzhong Zhang
Summary: Researchers have developed a new strategy for synthesizing amyloid proteins by fusing amyloid peptides with flexible linkers from spider silk proteins, resulting in fibers with strong mechanical properties. These fibers can be utilized for a variety of mechanically demanding applications, surpassing most recombinant protein fibers and even some natural spider silk fibers in terms of ultimate tensile strength and toughness.
Article
Multidisciplinary Sciences
Christopher H. Bowen, Cameron J. Sargent, Ao Wang, Yaguang Zhu, Xinyuan Chang, Jingyao Li, Xinyue Mu, Jonathan M. Galazka, Young-Shin Jun, Sinan Keten, Fuzhong Zhang
Summary: The study engineered microbial production of high-performance fibers with properties similar to natural titin, but with higher strength, toughness, and damping energy than many synthetic and natural polymers. The unique inter-chain crystallization of folded immunoglobulin-like domains is suggested to be the key to these superior properties, allowing resistance to interchain slippage while permitting intra-chain unfolding. These fibers have potential applications in fields ranging from biomedicine to textiles, and the developed approach is expected to spur further innovation in microbial production of high-performance materials.
NATURE COMMUNICATIONS
(2021)
Article
Nanoscience & Nanotechnology
Eugene Kim, Juya Jeon, Yaguang Zhu, Ethan D. Hoppe, Young-Shin Jun, Guy M. Genin, Fuzhong Zhang
Summary: A novel hybrid protein with strong underwater adhesion properties was designed and synthesized using synthetic biology approaches, demonstrating high strength, toughness, and selective debonding capabilities through oxidation or iron-chelating treatments. This material design and biosynthetic approach have the potential to inspire the development of a wide range of hybrid protein-based materials with tunable properties and broad applications.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Review
Biochemistry & Molecular Biology
Jingyao Li, Fuzhong Zhang
Summary: Amyloids are self-assembled protein aggregates with cross-beta fibrillar morphology. They are not only associated with diseases like Alzheimer's and Parkinson's, but also play important functional roles in diverse organisms. Amyloid fibrils' rigidity, chemical stability, high aspect ratio, and sequence programmability make them attractive for functional materials in environmental sciences, material engineering, and translational medicines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Christopher J. Hartline, Ruixue Zhang, Fuzhong Zhang
Summary: This study found that shifts in carbon sources and positive feedback in nutrient transport are not enough to trigger persistence in the majority of bacteria, but instead only lead to temporary tolerance. Additionally, the duration of this temporary tolerance is determined by the metabolic state prior to the shift, and supplying glyoxylate can facilitate antibiotic killing of bacteria.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemical Research Methods
Christopher J. Hartline, Fuzhong Zhang
Summary: Metabolite biosensors based on metabolite-responsive transcription factors are important components in synthetic biology for sensing and controlling cellular metabolism. This study investigates the impact of growth rate on biosensor performance and reveals that different biosensors exhibit different growth rate dependencies in their dynamic range. The study also develops a kinetic model to explore the effects of tuning biosensor parameters on dynamic range and its growth rate dependence.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Wenqin Bai, Winston E. Anthony, Christopher J. Hartline, Shaojie Wang, Bin Wang, Jie Ning, Fong-Fu Hsu, Gautam Dantas, Fuzhong Zhang
Summary: Bacterial fatty acids are essential components of cellular membranes and important sources of renewable chemicals. Modifying their structure can expand their applications and affect the growth and metabolic state of the producing cells. This study successfully engineered Escherichia coli to have different fatty acid profiles, and found that these profiles had varying effects on transcriptome, growth, and stress response.
METABOLIC ENGINEERING
(2022)
Article
Oncology
Richard J. Sove, Babita K. Verma, Hanwen Wang, Won Jin Ho, Mark Yarchoan, Aleksander S. Popel
Summary: This study uses quantitative systems pharmacology (QSP) framework to conduct a virtual clinical trial for nivolumab and ipilimumab in HCC patients. The model incorporates detailed biological mechanisms of immune cell-cancer cell interactions and generates virtual patients for the trial. The predictions of the model are consistent with clinically observed outcomes, demonstrating the potential of QSP models in patient selection and trial design.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Biochemistry & Molecular Biology
Juya Jeon, Shri Venkatesh Subramani, Kok Zhi Lee, Bojing Jiang, Fuzhong Zhang
Summary: High molecular weight (MW), highly repetitive protein polymers have the potential to replace petroleum-derived materials due to their renewable, biodegradable nature and exceptional mechanical properties. However, their synthesis in large quantities for real-world applications is challenging due to their high MW and repetitive sequence features. To address this challenge, various methods, including construction of repetitive genes, expression of repetitive proteins from circular mRNAs, and synthesis of repetitive proteins through ligation and protein polymerization, have been developed. This review discusses the advantages, limitations, and future directions for the scalable production of highly repetitive protein polymers for diverse applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jingyao Li, Bojing Jiang, Xinyuan Chang, Han Yu, Yichao Han, Fuzhong Zhang
Summary: The authors have developed a method to enhance the strength of low molecular-weight protein materials by fusing intrinsically-disordered mussel foot protein fragments. This approach can be applied to a wide range of protein-based materials and has the potential to achieve high yields.
NATURE COMMUNICATIONS
(2023)
Review
Chemistry, Analytical
Gloria J. Zhou, Fuzhong Zhang
Summary: TF-based biosensors are commonly used for metabolite detection and cellular pathway regulation. However, their direct application to new hosts or metabolic pathways often requires extensive tuning for optimal performance. This review highlights recent strategies for engineering TF-based biosensors to achieve desired performance and discusses additional design considerations. The article also examines applications of these sensors and suggests important areas for further research.
Review
Biotechnology & Applied Microbiology
Xinyue Mu, Fuzhong Zhang
Summary: This article provides a comprehensive overview of heterogeneity in microbial bioproduction, including its mechanisms and strategies for control. By understanding and controlling heterogeneity, economic competitiveness of biomanufacturing can be enhanced.
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Po-Cheng Lin, Fuzhong Zhang, Himadri B. Pakrasi
Summary: Terpenoids are a diverse group of natural products with commercial applications, and microbial production of terpenes in cyanobacteria is a promising approach. This study successfully engineered a cyanobacterium to produce limonene by identifying a beneficial mutation in a key gene, leading to a significant increase in production. Combinatorial metabolic engineering was used to optimize gene expression levels in the biosynthesis pathway, demonstrating the importance of fine-tuning gene expression for enhancing terpene production in cyanobacteria.
METABOLIC ENGINEERING COMMUNICATIONS
(2021)