Review
Engineering, Chemical
Ziheng Cui, Shiding Zhang, Shengyu Zhang, Biqiang Chen, Yushan Zhu, Tianwei Tan
Summary: Biomanufacturing, using renewable resources and biological processes, is seen as a sustainable alternative to the fossil fuel economy. Creating efficient biosynthesis routes for chemicals is a key goal in green biomanufacturing. With advancements in information technology, intelligent biomanufacturing offers hope in achieving this goal. Retrobiosynthesis and computational enzyme design, as two important technologies, have rapidly developed and shown potential for integration in this field.
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2022)
Article
Agricultural Engineering
Xueqin Lv, Wenwen Yu, Chenyang Zhang, Peng Ning, Jianghua Li, Yanfeng Liu, Guocheng Du, Long Liu
Summary: This paper summarizes and discusses current developments in C1 compounds for biomanufacturing. It introduces two primary groups of microbes that use C1 compounds and their traits, categorization, and functions. It compiles and reviews engineering strategies for C1 utilization, as well as highlights the uses of C1 compounds in the synthesis of biofuels and high-value compounds. Potential obstacles and future research initiatives in C1-based biomanufacturing are also discussed.
BIORESOURCE TECHNOLOGY
(2023)
Article
Engineering, Biomedical
Mark C. Allenby, Maria A. Woodruff
Summary: Industrial cell culture processes are expensive, time-consuming, and variable. Recent advances in biomedical image analysis and computational modeling provide opportunities to enhance the design and operation of tissue biomanufacturing platforms, improving efficiency and consistency. This review outlines current resources and approaches that utilize biomedical imaging and image-based computational models for efficient and robust human tissue biomanufacturing.
Review
Biochemical Research Methods
Dongming Xie
Summary: This review discusses the major challenges and strategies for continuous biomanufacturing, including minimizing contamination risk, enhancing genetic stability, decoupling cell growth from product formation, using modeling approach to accelerate research and development, and new strategies for intelligent and next-generation manufacturing.
CURRENT OPINION IN BIOTECHNOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Siyuan Gao, Yang Liao, Hao He, Huiling Yang, Xuewei Yang, Sheng Xu, Xin Wang, Kequan Chen, Pingkai Ouyang
Summary: Industrial microbes, as cell factories, face extreme stress conditions during production, making it essential to enhance their robustness for better tolerance. Improving cell robustness can be achieved through irrational and rational engineering strategies, including reshaping regulatory networks, modifying cell membranes, and other stress responses. This review provides a summary of metabolic engineering technologies for enhancing the tolerance of microbes to industrial conditions, and discusses the emerging ideas related to the development of biological instruments and synthetic biology.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Joan Planas-Iglesias, Sergio M. Marques, Gaspar P. Pinto, Milos Musil, Jan Stourac, Jiri Damborsky, David Bednar
Summary: Enzymes are natural catalysts that execute biochemical reactions, and their effectiveness has been optimized through evolution. Biocatalysts from various sources are used in industrial production, environmental protection, and biomedical applications. Protein engineering and computational techniques can improve enzyme function for diverse applications.
BIOTECHNOLOGY ADVANCES
(2021)
Article
Engineering, Biomedical
Gabriella Nilsson Hall, Iene Rutten, Jeroen Lammertyn, Jens Eberhardt, Liesbet Geris, Frank P. Luyten, Ioannis Papantoniou
Summary: This study investigates the assembly capacity of cartilaginous spheroids in endochondral bone formation and explores design considerations for engineered cartilaginous mesotissues. The influence of spheroid fusion parameters on endochondral ossification is studied, and a novel automated image-guided robotics process for producing spheroid-based implants for bone regeneration is demonstrated.
Article
Chemistry, Applied
Hsin-Tzu Wang, S. Vivek Bharadwaj, Jeong-Yeh Yang, M. Thomas Curry, W. Kelley Moremen, J. Yannick Bomble, R. Breeanna Urbanowicz
Summary: The study demonstrates the importance of the major lobe of XOAT1 for xylan binding, with mutation of key residues yielding variants with different enzymatic efficiencies. Computational modeling is effective in guiding enzyme engineering to modulate xylan and redesign plant cell walls.
CARBOHYDRATE POLYMERS
(2021)
Review
Biotechnology & Applied Microbiology
Zhongdi Song, Qunfeng Zhang, Wenhui Wu, Zhongji Pu, Haoran Yu
Summary: The strategy of rational design is to predict potential mutants based on the understanding of protein structure-function relationships and introduce mutations using site-directed mutagenesis. Rational design methods are universal, fast, and have the potential for quantitative prediction of designed sequence performance. Designing enzymes with improved activity or selectivity is challenging due to the complexity of enzyme structure and limited understanding of structure-function relationships. However, with computational advancement and deeper understanding of enzyme catalysis, rational design can simplify enzyme engineering and its application is increasing.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Xinglong Wang, Kangjie Xu, Yameng Tan, Song Liu, Jingwen Zhou
Summary: Food enzymes play a crucial role in improving food characteristics, such as texture, safety, carbohydrates production, and flavor/appearance enhancement. With the development of artificial meats, food enzymes are being utilized for more diverse functions, especially in converting non-edible biomass into edible foods. This article highlights the significance of enzyme engineering through de novo design, which provides potential solutions for screening desired enzymes. It discusses the functions and applications of food enzymes, reviews protein modeling and de novo design methods, and emphasizes future challenges in designing food enzymes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemical Research Methods
Bill Whitford, Daniel Jones, Sean Kinnane
Summary: Biopharmaceutical manufacturing aims to reduce its environmental footprint through science-based approaches and promote circular economies. Architecture and process design play a crucial role in reducing environmental stress while meeting expectations.
CURRENT OPINION IN BIOTECHNOLOGY
(2022)
Article
Agricultural Engineering
Weibo Qiao, Shijie Xu, Zihe Liu, Xiaoying Fu, Huimin Zhao, Shuobo Shi
Summary: This article reviews the methods of engineering microorganisms to fix and convert C1 compounds into metabolites that can serve as fuels and platform chemicals, and discusses the key factors and challenges for achieving C1-based biorefinery.
BIORESOURCE TECHNOLOGY
(2022)
Article
Physics, Applied
Talmage L. Coates, Naomi Young, Austin J. Jarrett, Connor J. Morris, James D. Moody, Dennis Della Corte
Summary: Computational enzyme design has become a powerful tool to predict the impact of mutations on protein properties, reducing in vitro workload and speeding up design process. Recent studies have reviewed the efficacy and differences of computational enzyme design methods, emphasizing on design objectives achieved and results verified in vitro.
MODERN PHYSICS LETTERS B
(2021)
Article
Chemistry, Multidisciplinary
Miaomiao Liu, Yunhong Song, Yi-Heng P. Job Zhang, Chun You
Summary: A method for carrier-free immobilization of multi-enzyme complexes with more than four enzymes is developed using polypeptide interactions and enzyme component self-oligomerization. The self-assembled enzyme complexes show higher initial reaction rates than the four-enzyme cocktail. Water-insoluble self-assembled multi-enzyme complexes are observed, serving as carrier-free immobilized multi-enzyme complex aggregates. These immobilized enzyme complexes can be easily recycled and obtained from either purified enzyme components or crude cell extracts. This strategy sheds light on improving the catalytic capability of in vitro synthetic enzymatic biosystems.
Article
Engineering, Biomedical
Evangelos Daskalakis, Fengyuan Liu, Boyang Huang, Anil A. Acar, Glen Cooper, Andrew Weightman, Gordon Blunn, Bahattin Koc, Paulo Bartolo
Summary: This study explores a novel osseointegrated prosthetic solution using modular bone bricks, investigating the impact of different architectures and material compositions on the performance of the prosthesis. Results showed that reinforced bone bricks with specific filament patterns exhibited improved mechanical and biological properties, with the best outcomes achieved with certain combinations of materials and structures.
INTERNATIONAL JOURNAL OF BIOPRINTING
(2021)
Article
Biochemistry & Molecular Biology
Edita Sarukhanyan, Thomas Dandekar
Summary: Microtubules are essential for maintaining cell shape and Tau protein plays a role in regulating their plasticity. Abnormal phosphorylation of Tau proteins leads to the formation of neurofibrillary tangles, which are linked to Alzheimer's disease. In this study, a potential drug candidate, compound 23, was designed using computer simulations to target the phosphorylated Tau-microtubule complexes. The results showed that compound 23 can bind to and stabilize phosphorylated Tau proteins on the surface of microtubules, preventing their aggregation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Patricia Gomez de Santos, Ivan Mateljak, Manh Dat Hoang, Sarel J. Fleishman, Frank Hollmann, Miguel Alcalde
Summary: In this study, a diverse repertoire of active, stable, and enantiodivergent fungal peroxidases was designed using the FuncLib algorithm based on phylogenetic and Rosetta calculations. Several designs showed unprecedented enantiodivergence, changing regioselectivity, and increasing catalytic efficiencies up to 10-fold, with improvements in total turnover numbers. Beneficial epistasis among the mutations and extensive reorganization of the heme channel contributed to this functional divergence. This work demonstrates the rapid design of highly functional peroxygenase libraries using FuncLib for various biotechnological applications, which are not naturally existing.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
R. Lipsh-Sokolik, O. Khersonsky, S. P. Schroder, C. de Boer, S. -Y. Hoch, G. J. Davies, H. S. Overkleeft, S. J. Fleishman
Summary: An atomistic and machine learning strategy called CADENZ was used to design enzyme fragments that combine to form diverse, low-energy structures with stable catalytic configurations. This strategy was applied to endoxylanases and resulted in the recovery of thousands of structurally diverse enzymes using activity-based protein profiling. Functional designs showed high active-site preorganization and more stable and compact packing outside the active site. Implementing these findings into CADENZ led to a 10-fold improved hit rate and over 10,000 recovered enzymes. This design-test-learn loop can be applied to any modular protein family, providing vast diversity and general principles for protein design.
Review
Biochemistry & Molecular Biology
Elena Bencurova, Aman Akash, Renwick C. J. Dobson, Thomas Dandekar
Summary: In this article, the fundamental aspects of DNA storage and recent advances in this field are discussed, with a focus on natural processes and solutions that can be utilized. New methods for efficient DNA and nucleotide storage inspired by nature are highlighted. Within a few years, DNA-based information storage may become a complement to current electronic data storage systems. Various aspects, such as rapid and directed access, regulatory signals and modulation, and integrated high-density storage and processing modules, are examined. DNA storage has practical applications in biotechnology and human genetics. The potential of DNA storage in synthetic biology and its advantages in direct storage operations are also explored. The use of biology concepts from chromosomal storage, nucleic acid processing, and polymer material sciences will lead to new applications gradually replacing classical information storage methods over time (decades).
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Chao Han, Pengxuan Ren, Medina Mamtimin, Linus Kruk, Edita Sarukhanyan, Chenyu Li, Hans-Joachim Anders, Thomas Dandekar, Irena Krueger, Margitta Elvers, Silvia Goebel, Kristin Adler, Goetz Muench, Thomas Gudermann, Attila Braun, Elmina Mammadova-Bach
Summary: This study analyzed the collagen- and CRP-binding surfaces of GPVI monomers and dimers using computational modeling and bioinformatics, and compared them with other mammalian GPVI isoforms. Experimental results show that the EA-20 antibody inhibits platelet adhesion and aggregation in response to collagen and CRP, but not to fibrin, and prevents thrombus formation in whole blood. Therefore, the blockade of this minimal collagen-binding epitope of GPVI with the EA-20 antibody could represent a new anti-thrombotic approach.
Article
Biochemistry & Molecular Biology
Sarka Pokorna, Olga Khersonsky, Rosalie Lipsh-Sokolik, Adi Goldenzweig, Rebekka Nielsen, Yacov Ashani, Yoav Peleg, Tamar Unger, Shira Albeck, Orly Dym, Asa Tirosh, Rana Tarayra, Michael Hocquemiller, Ralph Laufer, Shifra Ben-Dor, Israel Silman, Joel L. L. Sussman, Sarel J. J. Fleishman, Anthony H. H. Futerman
Summary: In this study, GCase variants with enhanced stability were generated using the PROSS stability-design algorithm. These variants showed improved enzymatic activity and could be used as an alternative to the recombinant human enzymes for treating Gaucher disease. Additionally, a machine learning-based approach was developed to predict the enzymatic activity of GBA1 gene variants, which could be used to determine disease risk factors in patients carrying rare mutations.
Article
Multidisciplinary Sciences
Gerard Duart, Assaf Elazar, Jonathan Y. Weinstein, Laura Gadea-Salom, Juan Ortiz-Mateu, Sarel J. Fleishman, Ismael Mingarro, Luis Martinez-Gil
Summary: Several methods have been developed to explore protein-protein interactions, but there is a need for more research on targeting transmembrane domains (TMDs). This study developed a computational approach to design sequences that can modulate protein-protein interactions in the membrane, and successfully applied it to BclxL. The findings enhance our understanding of protein-protein interactions in membranes and may lead to the development of inhibitors targeting TMD interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Fanindra Kumar Deshmukh, Gili Ben-Nissan, Maya A. Olshina, Maria G. Fuzesi-Levi, Caley Polkinghorn, Galina Arkind, Yegor Leushkin, Irit Fainer, Sarel J. Fleishman, Dan Tawfik, Michal Sharon
Summary: Controlled degradation of proteins is crucial for maintaining a healthy proteome. A family of proteins called Catalytic Core Regulators (CCRs) has been discovered to regulate the function of the 20S proteasome through an allosteric mechanism. The physical binding of the PSMB4 subunit attenuates the proteolytic activities of the proteasome. This finding sheds light on a novel allosteric pathway that can be targeted for developing selective 20S proteasome inhibitors and uncoupling the degradation pathways of 20S and 26S proteasomes.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Iris D. D. Zelnik, Beatriz Mestre, Jonathan J. J. Weinstein, Tamir Dingjan, Stav Izrailov, Shifra Ben-Dor, Sarel J. J. Fleishman, Anthony H. H. Futerman
Summary: Researchers validate a one-step algorithm called mPROSS for stabilizing membrane proteins directly from an AlphaFold2 model structure. By applying this algorithm to ceramide synthase, they obtained a more stable form of human CerS2 enzyme through 37 designed mutations. With the help of molecular dynamics simulations, a potential pathway for substrate delivery to ceramide synthases is proposed.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Kunkun Li, Juan Prada, Thomas Dandekar, Daniel S. C. Damineli, Kai R. R. Konrad
Summary: The polar growth and guidance of pollen tubes are regulated by chemical and electrical signaling cues. The functional relationship between membrane voltage (V-m), Ca2+, and H+ dynamics in pollen tubes is largely unclear. In this study, live-cell imaging and cross-correlation analysis revealed distinct relationships between these signals along pollen tubes, with Ca2+ and H+ correlating with V-m dynamics at the tip, while only H+ correlated with V-m at the shank. These findings suggest spatially confined chemo-electric coupling supports the propagation of voltage and pH waves along non-growing pollen tubes, preceded by short-lasting but high amplitude tip Ca2+ spikes.
Article
Biochemistry & Molecular Biology
Aylin Caliskan, Deniz Caliskan, Lauritz Rasbach, Weimeng Yu, Thomas Dandekar, Tim Breitenbach
Summary: Machine learning techniques are widely used to analyze single-cell expression data, impacting various fields such as cell annotation, clustering, and signature identification. This framework evaluates gene selection sets based on their ability to effectively separate defined phenotypes or cell groups. It overcomes the limitation of identifying a small gene set with high information content for phenotype separation, and provides corresponding code scripts. The selected subset of genes facilitates human interpretability of phenotype differences, and can potentially explain the causal relationships between genes and phenotypes.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Rana Salihoglu, Mugdha Srivastava, Chunguang Liang, Klaus Schilling, Aladar Szalay, Elena Bencurova, Thomas Dandekar
Summary: PRO-Simat is a simulation tool that analyzes protein interaction networks, their dynamic changes, and pathway engineering. It provides GO enrichment, KEGG pathway analyses, and network visualization using a database of over 8 million protein-protein interactions across 32 organisms. The tool also allows for dynamical network simulation using the Jimena framework, offering in-depth analysis of protein interactions. It has demonstrated applications in understanding differentiation pathways, oncolytic virus development, and optogenetic control of nucleotide processing protein networks. PRO-Simat can be accessed at https://prosimat.heinzelab.de/ as a web-based query server.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Patricia Gomez de Santos, Ivan Mateljak, Manh Dat Hoang, Sarel J. Fleishman, Frank Hollmann, Miguel Alcalde
Summary: In this study, we used the FuncLib algorithm based on phylogenetic and Rosetta calculations to design a diverse repertoire of active, stable, and enantiodivergent fungal perox-ygenases. These designs, which carried 4-5 mutations in the catalytic core, were functionally expressed in yeast and showed remarkable improvements in catalytic efficiency and enantiodivergence compared to the parental enzyme. The functional divergence was attributed to beneficial epistasis among the mutations and extensive reorganization of the heme channel. This work highlights the potential of FuncLib in designing highly functional libraries of enantioselective peroxygenases for biotechnological applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Biochemistry & Molecular Biology
Aylin Caliskan, Seema Dangwal, Thomas Dandekar
Summary: In the rapidly evolving field of biomedical research, the emergence of big data has provided researchers with opportunities to explore biological complexities. However, to ensure the reliability and reproducibility of data-driven findings, it is crucial to have detailed and accurate metadata.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Medical Laboratory Technology
Nora Vogg, Tobias Mueller, Andreas Floren, Thomas Dandekar, Oliver Scherf-Clavel, Martin Fassnacht, Matthias Kroiss, Max Kurlbaum
Summary: In this study, a sensitive and robust LC-MS/MS method for the quantification of 11 urinary steroids was developed and validated. The pre-analytical matrix stability was evaluated and the suitability of the method for the analysis of clinical samples and prospective validation studies was demonstrated.
JOURNAL OF MASS SPECTROMETRY AND ADVANCES IN THE CLINICAL LAB
(2022)
