Annual Review of Chemical and Biomolecular Engineering

Reassessing the Standard Chemotaxis Framework for Understanding Biased Migration in
Antani JD, Shaji A, Gupta R and Lele PP
infections are a major cause of peptic ulcers and gastric cancers. The development of robust inflammation in response to these flagellated, motile bacteria is correlated with poor prognosis. Chemotaxis plays a crucial role in colonization, enabling the bacteria to swim toward favorable chemical environments. Unlike the model species of bacterial chemotaxis, , cells possess polar flagella. They run forward by rotating their flagella counterclockwise, whereas backward runs are achieved by rotating their flagella clockwise. We delve into the implications of certain features of the canonical model of chemotaxis on our understanding of biased migration in polarly flagellated bacteria such as . In particular, we predict how the translational displacement of cells during a backward run could give rise to chemotaxis errors within the canonical framework. Also, lack key chemotaxis enzymes found in , without which sensitive detection of ligands with a wide dynamic range seems unlikely. Despite these problems, exhibit robust ability to migrate toward urea-rich sources. We emphasize various unresolved questions regarding the biophysical mechanisms of chemotaxis in , shedding light on potential directions for future research. Understanding the intricacies of biased migration in could offer valuable insights into how pathogens breach various protective barriers in the human host.
Biofilms for Production of Chemicals and Energy
Weiler J, Edel M and Gescher J
The twenty-first century will be the century of biology. This is not only because of breakthrough advances in molecular biology tools but also because we need to reinvent our economy based on the biological principles of energy efficiency and sustainability. Consequently, new tools for production routines must be developed to help produce platform chemicals and energy sources based on sustainable resources. In this context, biofilm-based processes have the potential to impact future production processes, because they can be carried out continuously and with robust stationary biocatalysts embedded in an extracellular matrix with different properties. We review productive biofilm systems used for heterotrophic and lithoautotrophic production and attempt to identify fundamental reasons why they may be particularly suitable as future production systems.
Accelerating Diverse Cell-Based Therapies Through Scalable Design
Peterman EL, Ploessl DS and Galloway KE
Augmenting cells with novel, genetically encoded functions will support therapies that expand beyond natural capacity for immune surveillance and tissue regeneration. However, engineering cells at scale with transgenic cargoes remains a challenge in realizing the potential of cell-based therapies. In this review, we introduce a range of applications for engineering primary cells and stem cells for cell-based therapies. We highlight tools and advances that have launched mammalian cell engineering from bioproduction to precision editing of therapeutically relevant cells. Additionally, we examine how transgenesis methods and genetic cargo designs can be tailored for performance. Altogether, we offer a vision for accelerating the translation of innovative cell-based therapies by harnessing diverse cell types, integrating the expanding array of synthetic biology tools, and building cellular tools through advanced genome writing techniques.
Fluid Ejections in Nature
Challita EJ, Rohilla P and Bhamla MS
From microscopic fungi to colossal whales, fluid ejections are universal and intricate phenomena in biology, serving vital functions such as animal excretion, venom spraying, prey hunting, spore dispersal, and plant guttation. This review delves into the complex fluid physics of ejections across various scales, exploring both muscle-powered active systems and passive mechanisms driven by gravity or osmosis. It introduces a framework using dimensionless numbers to delineate transitions from dripping to jetting and elucidate the governing forces. Highlighting the understudied area of complex fluid ejections, this review not only rationalizes the biophysics involved but also uncovers potential engineering applications in soft robotics, additive manufacturing, and drug delivery. By bridging biomechanics, the physics of living systems, and fluid dynamics, this review offers valuable insights into the diverse world of fluid ejections and paves the way for future bioinspired research across the spectrum of life.
Biological Upcycling of Plastics Waste
Klauer RR, Hansen DA, Wu D, Monteiro LMO, Solomon KV and Blenner MA
Plastic wastes accumulate in the environment, impacting wildlife and human health and representing a significant pool of inexpensive waste carbon that could form feedstock for the sustainable production of commodity chemicals, monomers, and specialty chemicals. Current mechanical recycling technologies are not economically attractive due to the lower-quality plastics that are produced in each iteration. Thus, the development of a plastics economy requires a solution that can deconstruct plastics and generate value from the deconstruction products. Biological systems can provide such value by allowing for the processing of mixed plastics waste streams via enzymatic specificity and using engineered metabolic pathways to produce upcycling targets. We focus on the use of biological systems for waste plastics deconstruction and upcycling. We highlight documented and predicted mechanisms through which plastics are biologically deconstructed and assimilated and provide examples of upcycled products from biological systems. Additionally, we detail current challenges in the field, including the discovery and development of microorganisms and enzymes for deconstructing non-polyethylene terephthalate plastics, the selection of appropriate target molecules to incentivize development of a plastic bioeconomy, and the selection of microbial chassis for the valorization of deconstruction products.
Advanced Modeling and Optimization Strategies for Process Synthesis
Pistikopoulos EN and Tian Y
This article provides a systematic review of recent progress in optimization-based process synthesis. First, we discuss multiscale modeling frameworks featuring targeting approaches, phenomena-based modeling, unit operation-based modeling, and hybrid modeling. Next, we present the expanded scope of process synthesis objectives, highlighting the considerations of sustainability and operability to assure cost-competitive production in an increasingly dynamic market with growing environmental awareness. Then, we review advances in optimization algorithms and tools, including emerging machine learning-and quantum computing-assisted approaches. We conclude by summarizing the advances in and perspectives for process synthesis strategies.
CRISPR Tools for Engineering Prokaryotic Systems: Recent Advances and New Applications
Burbano DA, Kiattisewee C, Karanjia AV, Cardiff RAL, Faulkner ID, Sugianto W and Carothers JM
In the past decades, the broad selection of CRISPR-Cas systems has revolutionized biotechnology by enabling multimodal genetic manipulation in diverse organisms. Rooted in a molecular engineering perspective, we recapitulate the different CRISPR components and how they can be designed for specific genetic engineering applications. We first introduce the repertoire of Cas proteins and tethered effectors used to program new biological functions through gene editing and gene regulation. We review current guide RNA (gRNA) design strategies and computational tools and how CRISPR-based genetic circuits can be constructed through regulated gRNA expression. Then, we present recent advances in CRISPR-based biosensing, bioproduction, and biotherapeutics across in vitro and in vivo prokaryotic systems. Finally, we discuss forthcoming applications in prokaryotic CRISPR technology that will transform synthetic biology principles in the near future.
Critical Mineral Separations: Opportunities for Membrane Materials and Processes to Advance Sustainable Economies and Secure Supplies
Lair L, Ouimet JA, Dougher M, Boudouris BW, Dowling AW and Phillip WA
Sustainable energy solutions and electrification are driving increased demand for critical minerals. Unfortunately, current mineral processing techniques are resource intensive, use large quantities of hazardous chemicals, and occur at centralized facilities to realize economies of scale. These aspects of existing technologies are at odds with the sustainability goals driving increased demand for critical minerals. Here, we argue that the small footprint and modular nature of membrane technologies position them well to address declining concentrations in ores and brines, the variable feed concentrations encountered in recycling, and the environmental issues associated with current separation processes; thus, membrane technologies provide new sustainable pathways to strengthening resilient critical mineral supply chains. The success of creating circular economies hinges on overcoming diverse barriers across the molecular to infrastructure scales. As such, solving these challenges requires the convergence of research across disciplines rather than isolated innovations.
Models for Decarbonization in the Chemical Industry
Yao Y, Lan K, Graedel TE and Rao ND
Various technologies and strategies have been proposed to decarbonize the chemical industry. Assessing the decarbonization, environmental, and economic implications of these technologies and strategies is critical to identifying pathways to a more sustainable industrial future. This study reviews recent advancements and integration of systems analysis models, including process analysis, material flow analysis, life cycle assessment, techno-economic analysis, and machine learning. These models are categorized based on analytical methods and application scales (i.e., micro-, meso-, and macroscale) for promising decarbonization technologies (e.g., carbon capture, storage, and utilization, biomass feedstock, and electrification) and circular economy strategies. Incorporating forward-looking, data-driven approaches into existing models allows for optimizing complex industrial systems and assessing future impacts. Although advances in industrial ecology-, economic-, and planetary boundary-based modeling support a more holistic systems-level assessment, more efforts are needed to consider impacts on ecosystems. Effective applications of these advanced, integrated models require cross-disciplinary collaborations across chemical engineering, industrial ecology, and economics.
Will Hydrogen Be a New Natural Gas? Hydrogen Integration in Natural Gas Grids
Linke G
Hydrogen is similar to natural gas in terms of its physical and chemical properties but does not release carbon dioxide when burnt. This makes hydrogen an energy carrier of great importance in climate policy, especially as an enabler of increasing integration of volatile renewable energy, progressive electrification, and effective emission reductions in the hard-to-decarbonize sectors. Leaving aside the problems of transporting hydrogen as a liquid, technological challenges along the entire supply chain can be considered as solved in principle, as shown in the experimental findings of the Hydrogen Innovation Program of the German Technical and Scientific Association for Gas and Water. By scaling up production and end-use capacities and, most importantly, producing hydrogen in regions with abundant renewable energy, hydrogen and its applications can displace natural gas at affordable prices in the medium term. However, this substitution will take place at different rates in different regions and with different levels of added value, all of which must be understood for hydrogen uptake to be successful.
Deductive Machine Learning Challenges and Opportunities in Chemical Applications
Jin T and Savoie BM
Contemporary machine learning algorithms have largely succeeded in automating the development of mathematical models from data. Although this is a striking accomplishment, it leaves unaddressed the multitude of scenarios, especially across the chemical sciences and engineering, where deductive, rather than inductive, reasoning is required and still depends on manual intervention by an expert. This review describes the characteristics of deductive reasoning that are helpful for understanding the role played by expert intervention in problem-solving and explains why such interventions are often relatively resistant to disruption by typical machine learning strategies. The article then discusses the factors that contribute to creating a deductive bottleneck, how deductive bottlenecks are currently addressed in several application areas, and how machine learning models capable of deduction can be designed. The review concludes with a tutorial case study that illustrates the challenges of deduction problems and a notebook for readers to experiment with on their own.
Design of Coiled-Coil Protein Nanostructures for Therapeutics and Drug Delivery
Britton D, Sun JW, Renfrew PD and Montclare JK
Coiled-coil protein motifs have become widely employed in the design of biomaterials. Some of these designs have been studied for use in drug delivery due to the unique ability of coiled-coils to impart stability, oligomerization, and supramolecular assembly. To leverage these properties and improve drug delivery, release, and targeting, a variety of nano- to mesoscale architectures have been adopted. Coiled-coil drug delivery and therapeutics have been developed by using the coiled-coil alone, designing for higher-order assemblies such as fibers and hydrogels, and combining coiled-coil proteins with other biocompatible structures such as lipids and polymers. We review the recent development of these structures and the design criteria used to generate functional proteins of varying sizes and morphologies.
Multifunctional Material Building Blocks from Plant Pollen
Zhou C, Deng J, Hao TJ, Basu S, Yang J, Li J, Yang C, Zhao Z and Cho NJ
With its multifaceted nature, plant pollen serves not only as a key element in the reproductive cycle of seed plants but also as an influential contributor to environmental, human health, safety, and climate-related concerns. Pollen functions as a carrier of nutrients and organisms and holds a pivotal role in sustaining pollinator populations. Moreover, it is vital in ensuring the safety and quality of our food supply while presenting potential therapeutic applications. Pollen, often referred to as the diamond of the organic world due to its distinctive physical structures and properties, has been underappreciated from a material science and engineering standpoint. We propose adopting a more interdisciplinary and comprehensive approach to its study. Recent groundbreaking research has focused on the development of pollen-based building blocks that transform practically indestructible plant pollen into microgel, paper, and sponge, thereby unveiling numerous potential applications. In this review, we highlight the transformative potential of plant pollen as it is converted into a variety of building blocks, thereby unlocking myriad prospective applications through eco-friendly processing.
Periodic Open Cellular Structures in Chemical Engineering: Application in Catalysis and Separation Processes
Eckendörfer L, Rudolf D, Brix A, Börnhorst M and Freund H
Periodic open cellular structures (POCS) represent a promising new class of structured internals as next-generation catalyst supports in reactors or structured packing elements in separation columns. POCS feature a well-defined morphology and can be fabricated with high reproducibility even for complex geometries by means of additive manufacturing. This results in a uniform and easily controllable flow field, which allows for adjusting the heat and mass transport processes to realize optimal process conditions. We review the fundamentals of POCS, including design and manufacturing as well as transport phenomena for single- and multiphase systems. Moreover, we review recent POCS applications in reaction and separation processes and consider promising future application fields. The exceptional transport characteristics of POCS facilitate the design of highly efficient, flexible, resilient, and safe processes, which is key for achieving process intensification toward a sustainable future.
Three-Dimensional Morphology of Polymeric Membranes from Electron Tomography
Ghasemi M, Geitner M, O'Connell A and Gomez ED
Recent advances in the water-energy landscape hinge upon our improved understanding of the complex morphology of materials involved in water treatment and energy production. Due to their versatility and tunability for applications ranging from drug delivery to fuel cells, polymeric systems will play a crucial role in shaping the future of water-energy nexus applications. Electron tomography (ET) stands as a transformative approach for elucidating the intricate structures inherent to polymers, offering unparalleled insights into their nanoscale architectures and functional properties in three dimensions. In particular, the various morphological and chemical characteristics of polymer membranes provide opportunities for perturbations to standard ET for the study of these systems. We discuss the applications of transmission electron microscopy in establishing structure-function relationships in polymeric membranes with an emphasis on traditional ET and cryogenic ET (cryo-ET). The synergy between ET and cryo-ET to unravel structural complexities and dynamic behaviors of polymer membranes holds immense potential in driving progress and innovation across frontiers related to water-energy nexus applications. Expected final online publication date for the , Volume 15 is June 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Mechanism-Driven Design of Multispecific Antibodies for Targeted Disease Treatment
Fine J, Meksiriporn B, Tan J and Spangler JB
Antibody-based therapeutics constitute a rapidly growing class of pharmaceutical compounds. However, monoclonal antibodies, which specifically engage only one target, often lack the mechanistic intricacy to treat complex diseases. To expand the utility of antibody therapies, significant efforts have been invested in designing multispecific antibodies, which engage multiple targets using a single molecule. These efforts have culminated in remarkable translational progress, including nine US Food and Drug Administration-approved multispecific antibodies, with countless others in various stages of preclinical or clinical development. In this review, we discuss several categories of multispecific antibodies that have achieved clinical approval or shown promise in earlier stages of development. We focus on the molecular mechanisms used by multispecific antibodies and how these mechanisms inform their customized design and formulation. In particular, we discuss multispecific antibodies that target multiple disease markers, multiparatopic antibodies, and immune-interfacing antibodies. Overall, these innovative multispecific antibody designs are fueling exciting advances across the immunotherapeutic landscape. Expected final online publication date for the , Volume 15 is June 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Designing Multivalent and Multispecific Biologics
Kang JJ, Ohoka A and Sarkar CA
In the era of precision medicine, multivalent and multispecific therapeutics present a promising approach for targeted disease intervention. These therapeutics are designed to interact with multiple targets simultaneously, promising enhanced efficacy, reduced side effects, and resilience against drug resistance. We dissect the principles guiding the design of multivalent biologics, highlighting challenges and strategies that must be considered to maximize therapeutic effect. Engineerable elements in multivalent and multispecific biologic design-domain affinities, valency, and spatial presentation-must be considered in the context of the molecular targets as well as the balance of important properties such as target avidity and specificity. We illuminate recent applications of these principles in designing protein and cell therapies and identify exciting future directions in this field, underscored by advances in biomolecular and cellular engineering and computational approaches. Expected final online publication date for the , Volume 15 is June 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Engineering Innovations, Challenges, and Opportunities for Lignocellulosic Biorefineries: Leveraging Biobased Polymer Production
Shapiro AJ, O'Dea RM, Li SC, Ajah JC, Bass GF and Epps TH
Alternative polymer feedstocks are highly desirable to address environmental, social, and security concerns associated with petrochemical-based materials. Lignocellulosic biomass (LCB) has emerged as one critical feedstock in this regard because it is an abundant and ubiquitous renewable resource. LCB can be deconstructed to generate valuable fuels, chemicals, and small molecules/oligomers that are amenable to modification and polymerization. However, the diversity of LCB complicates the evaluation of biorefinery concepts in areas including process scale-up, production outputs, plant economics, and life-cycle management. We discuss aspects of current LCB biorefinery research with a focus on the major process stages, including feedstock selection, fractionation/deconstruction, and characterization, along with product purification, functionalization, and polymerization to manufacture valuable macromolecular materials. We highlight opportunities to valorize underutilized and complex feedstocks, leverage advanced characterization techniques to predict and manage biorefinery outputs, and increase the fraction of biomass converted into valuable products.
Nonconjugated Redox-Active Polymers: Electron Transfer Mechanisms, Energy Storage, and Chemical Versatility
Ma T, Easley AD, Thakur RM, Mohanty KT, Wang C and Lutkenhaus JL
The storage of electric energy in a safe and environmentally friendly way is of ever-growing importance for a modern, technology-based society. With future pressures predicted for batteries that contain strategic metals, there is increasing interest in metal-free electrode materials. Among candidate materials, nonconjugated redox-active polymers (NC-RAPs) have advantages in terms of cost-effectiveness, good processability, unique electrochemical properties, and precise tuning for different battery chemistries. Here, we review the current state of the art regarding the mechanisms of redox kinetics, molecular design, synthesis, and application of NC-RAPs in electrochemical energy storage and conversion. Different redox chemistries are compared, including polyquinones, polyimides, polyketones, sulfur-containing polymers, radical-containing polymers, polyphenylamines, polyphenazines, polyphenothiazines, polyphenoxazines, and polyviologens. We close with cell design principles considering electrolyte optimization and cell configuration. Finally, we point to fundamental and applied areas of future promise for designer NC-RAPs.
Introduction
Doherty MF, Segalman RA and Kane RS
RNAs as Sensors of Oxidative Stress in Bacteria
Buchser R, Sweet P, Anantharaman A and Contreras L
Oxidative stress is an important and pervasive physical stress encountered by all kingdoms of life, including bacteria. In this review, we briefly describe the nature of oxidative stress, highlight well-characterized protein-based sensors (transcription factors) of reactive oxygen species that serve as standards for molecular sensors in oxidative stress, and describe molecular studies that have explored the potential of direct RNA sensitivity to oxidative stress. Finally, we describe the gaps in knowledge of RNA sensors-particularly regarding the chemical modification of RNA nucleobases. RNA sensors are poised to emerge as an essential layer of understanding and regulating dynamic biological pathways in oxidative stress responses in bacteria and, thus, also represent an important frontier of synthetic biology.