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Microbial biomineralization is a phenomenon involving deposition of inorganic minerals inside or around microbial cells as a direct consequence of biogeochemical cycling. The microbial metabolic processes often create environmental conditions conducive for the precipitation of silicate, carbonate or phosphate, ferrate forms of ubiquitous inorganic ions. Till date the fundamental mechanisms underpinning two of the major types of microbial biomineralization such as, microbially controlled and microbially induced remains poorly understood. While microbially-controlled mineralization (MCM) depends entirely on the genetic makeup of the cell, microbially-induced mineralization (MIM) is dependent on factors such as cell morphology, cell surface structures and extracellular polymeric substances (EPS). In recent years, the organic template-mediated nucleation of inorganic minerals has been considered as an underlying mechanism based on the principles of solid-state bioinorganic chemistry. The present review thus attempts to provide a comprehensive and critical overview on the recent progress in holistic understanding of both MCM and MIM, which involves, organic–inorganic biomolecular interactions that lead to template formation, biomineral nucleation and crystallization. Also, the operation of specific metabolic pathways and molecular operons in directing microbial biomineralization have been discussed. Unravelling these molecular mechanisms of biomineralization can help in the biomimetic synthesis of minerals for potential therapeutic applications, and facilitating the engineering of microorganisms for commercial production of biominerals. [ABSTRACT FROM AUTHOR]

The functionalization of proteins with DNA through the formation of covalent bonds enables a wide range of biotechnology advancements. For example, single-molecule analytical methods rely on bioconjugated DNA as elastic biolinkers for protein immobilization. Labeling proteins with DNA enables facile protein identification, as well as spatial and temporal organization and control of protein within DNA–protein networks. Bioconjugation reactions can target native, engineered, and non-canonical amino acids (NCAAs) within proteins. In addition, further protein engineering via the incorporation of peptide tags and self-labeling proteins can also be used for conjugation reactions. The selection of techniques will depend on application requirements such as yield, selectivity, conjugation position, potential for steric hindrance, cost, commercial availability, and potential impact on protein function. The formation of covalent bonds between proteins and DNA has become an important step in a number of emerging biotechnological applications. Native amino acids can be targeted for DNA conjugation, however, this approach can suffer from poor selectivity. Protein engineering, ranging from single site-directed amino acid changes, to non-canonical amino acid incorporation, to the creation of fusion proteins, can be used to increase conjugation selectivities. More advanced conjugation strategies have been developed but these can require expensive oligonucleotide modifications and can suffer from lower yields. The optimal conjugation technique for each application may differ based on limiting factors such as yield, selectivity, flexibility in conjugation position, steric hindrance, cost, commercial availability of oligonucleotides, and risk of altering native protein properties. [ABSTRACT FROM AUTHOR]

Synthetic biology's multiscale approaches to biosensing facilitate biological detection across diverse environments, leading to the development of advanced bio/electronic devices that convert biological events into electrical signals. Electrochemical biosensors are particularly promising due to their cost-effectiveness, ease of fabrication, and potential for miniaturization. Cell-free synthetic biology (CFSB) utilizes cell-free biological components to engineer and mimic the behavior, functions, and characteristics of cell systems, providing versatile approaches to bioengineering beyond cellular contexts. Engineering electrode surface with the principles of CFSB systems may represent a cutting-edge research direction for electrochemical biosensing, potentially solving bioanalytical issues of selectivity, sensitivity, and biocompatibility. This review highlights the latest trends in creating biosensing electrodes with CFSB components, as categorized by transcriptional, translational, and novel CFSB types. It provides a comprehensive analysis of the benefits and challenges of engineering CFSB components on electrode surfaces, aiming to inspire the future integration of CFSB technologies into electrochemical biosensing research. • Description of the role of cell-free synthetic biology (CFBS) system for bioelectronic surface engineering. • Categorizing and discussing advantages and challenges the CFSB systems for the development of electrochemical biosensors. • Providing new insights on biomolecular engineering of electrode surface for enhanced bioanalytical performance. [ABSTRACT FROM AUTHOR]

Classical hydrogen bonds have, for many decades, been the dominant non‐covalent interaction in the toolbox that chemists and chemical engineers have used to design and control the structures of compounds and molecular assemblies as novel materials. Recently, a set of non‐classical non‐covalent (NC−NC) interactions have emerged that exploit the properties of the Group IV, V, VI, and VII elements of the periodic table (the tetrel, pnictogen, chalcogen, and halogen bonds, respectively). Our research group has been characterizing the prevalence, geometric constraints, and structure‐function relationship specifically of the halogen bond in biological systems. We have been particularly interested in exploiting the biological halogen bonds (or BXBs) to control the structures, stabilities, and activities of biomolecules, including the DNA Holliday junction and enzymes. In this review, we first provide a set of criteria for how to determine whether BXBs or any other NC−NC interactions would have biological relevance. We then navigate the trail of studies that had led us from an initial, very biological question to our current point in the journey to establish BXBs as a tool for biomolecular engineering. Finally, we close with a perspective on future directions for this line of research. [ABSTRACT FROM AUTHOR]

Keywords: biomolecular engineering; early detection; molecular biomedicine; molecular diagnosis; prognosis EN biomolecular engineering early detection molecular biomedicine molecular diagnosis prognosis 1 4 4 05/27/20 20200601 NES 200601 Introduction For the past nine years, Royan Institute (Tehran, Iran) has held annual international summer schools to educate and promote key basic and applied concepts regarding stem cells, cancer, personalized medicine, tissue engineering, and developmental biology. The speakers discussed genome-editing technologies, gene- and RNA interference (RNAi) therapies, cancer vaccines, and molecular diagnosis via biomarkers and biosensors. Overall, the summer school highlighted how combination of molecular diagnosis and molecular therapy can provide higher success rates in disease treatment in the near future. Viral and Non-Viral Gene Therapy Piter Bosma explained that gene therapy, that is, delivering genetic material to treat diseases, is accomplished through non-viral or viral delivery systems. [Extracted from the article]

Fungi are a prolific source of bioactive compounds, some of which have been developed as essential medicines and life-enhancing drugs. Genome sequencing has revealed that fungi have the potential to produce considerably more natural products (NPs) than are typically observed in the laboratory. Recently, there have been significant advances in the identification, understanding, and engineering of fungal biosynthetic gene clusters (BGCs). This review briefly describes examples of the engineering of fungal NP biosynthesis at the global, pathway, and enzyme level using in vivo and in vitro approaches and refers to the range and scale of heterologous expression systems available, developments in combinatorial biosynthesis, progress in understanding how fungal BGCs are regulated, and the applications of these novel biosynthetic enzymes as biocatalysts. Highlights The antibiotic penicillin revolutionized human medicine, and now fungal natural products (NPs) play a prominent role in the pharmaceutical and healthcare industries. Fungal genomes host a wealth of biosynthetic gene clusters (BGCs) that are silent under conventional laboratory culture conditions due to their tight regulation. Widely applicable methods have been developed to activate or modify these BGCs in both native and heterologous hosts and scalable expression platforms have been established. Fungal BGCs can be engineered to reveal biosynthetic intermediates or increase titers of NPs or combined with biosynthetic pathways from other species and/or other organisms to generate 'unnatural' NPs. Investigation of fungal BGCs often reveals unique enzymes with novel activities that can be applied to a plethora of unnatural substrates and developed as biocatalysts. [ABSTRACT FROM AUTHOR]

The recent recognition that halogen bonding (XB) plays important roles in the recognition and assembly of biological molecules has led to new approaches in medicinal chemistry and biomolecular engineering. When designing XBs into strategies for rational drug design or into a biomolecule to affect its structure and function, we must consider the relationship between this interaction and the more ubiquitous hydrogen bond (HB). In this review, we explore these relationships by asking whether and how XBs can replace, compete against or behave independently of HBs in various biological systems. The complex relationships between the two interactions inform us of the challenges we face in fully utilizing XBs to control the affinity and recognition of inhibitors against their therapeutic targets, and to control the structure and function of proteins, nucleic acids and other biomolecular scaffolds. [ABSTRACT FROM AUTHOR]

Engineering materials using supramolecular principles enables generalizable and modular platforms that have tunable chemical, mechanical, and biological properties. Applying this bottom-up, molecular engineering-based approach to therapeutic design affords unmatched control of emergent properties and functionalities. In preparing responsive materials for biomedical applications, the dynamic character of typical supramolecular interactions facilitates systems that can more rapidly sense and respond to specific stimuli through a fundamental change in material properties or characteristics, as compared to cases where covalent bonds must be overcome. Several supramolecular motifs have been evaluated toward the preparation of 'smart' materials capable of sensing and responding to stimuli. Triggers of interest in designing materials for therapeutic use include applied external fields, environmental changes, biological actuators, applied mechanical loading, and modulation of relative binding affinities. In addition, multistimuli-responsive routes can be realized that capture combinations of triggers for increased functionality. In sum, supramolecular engineering offers a highly functional strategy to prepare responsive materials. Future development and refinement of these approaches will improve precision in material formation and responsiveness, seek dynamic reciprocity in interactions with living biological systems, and improve spatiotemporal sensing of disease for better therapeutic deployment. [ABSTRACT FROM AUTHOR]

Being a natural polymer, DNA attracts extensive attention and possesses great potential to open a new way for researches of biomedical or material science. In the past few decades, approaches have been developed to bring DNA into the realm of bulk materials. In this review, we discussed the progresses achieved for fabrication of novel materials with a large physical dimension from the DNA polymer. [ABSTRACT FROM AUTHOR]

Abstract: The engineering of biological systems requires a set of molecular tools that can be predictably applied to the design of sophisticated genetic systems. Recent advances in the field of RNA synthetic biology, particularly in the design of synthetic regulatory RNAs for the static and dynamic control of gene expression, have increased our ability to efficiently build various biological systems capable of performing programmed cellular behaviors. Furthermore, implementing these synthetic regulatory RNAs in biological systems highlights the potential for designing synthetic cell systems for chemical synthesis, environmental, agricultural, and medical applications. In this paper, we review current developments in synthetic regulatory RNAs for the static and dynamic control of gene expression and the potential applications of these tools. [Copyright &y& Elsevier]

Highlights: [•] Helix 190 (H190) from influenza virus modularized onto unrelated polyomavirus VLP. [•] Antigen module design affected response quality (level of binding to HA1). [•] Flanking H190 element with GCN4 gave a low-quality response (low HA1 binding). [•] Modularizing multiple tandem repeats of H190 gave a high-quality antibody response. [•] Biomolecular engineering offers a future alternative to whole pathogen vaccines. [ABSTRACT FROM AUTHOR]

Abstract: Synthetic Biology offers qualitatively new perspectives on the benefits of industrially harnessed biological processes. The ability to modify and reprogramme natural biology increases the scope of tailored bioprocesses and yields attractive prospects beyond conventional Biotechnology. The present review summarises the major achievements and categorises them according to a hierarchy of system levels. Similar structures are known in the engineering sciences and might prove useful for the future development of Synthetic Biology. The hierarchy encompasses several levels of detail. Biological (macro-)molecules present the most detailed level (parts), followed by compartmentalised or non-compartmentalised modules (devices). In the next level, parts and devices are combined into functional cells and further into cellular communities. The manifold interactions between biological entities of the same hierarchical level or between different levels are accounted for by networks, primarily metabolic pathways and regulatory circuits. Networks of different types are represented as a superordinate hierarchical level that achieves full system integration. On all these levels, extensive and sound scientific foundations exist regarding experimental but also theoretical methods. These have led to diverse manifestations of Synthetic Biology on the parts and devices levels. Investigations involving synthetic components on the systems scale represent the most difficult and remain limited in number. A main challenge lies with the quantitative prediction of interactions between different entities across different scales. Systems-theoretical approaches provide important tools to analyse complex biological behaviour and can support the design of artificial biological systems. A promising strategy is seen in an efficient modularisation that reduces biological systems to a limited set of functional modules with well-characterised interfaces. For the design of synthetic biological systems the interactions across these interfaces should be standardised to reduce complexity. Yet, the identification of modules and standardised interaction routes remains a non-trivial problem. Furthermore, an appropriate platform that efficiently describes replication and evolutionary processes has to be developed in order to extend the achievements of Synthetic Biology into designed biological processes. [Copyright &y& Elsevier]

Artificial chemistries are candidates for methodologies that model and design biochemical systems. If artificial chemistries can deal with such systems in beneficial ways, they may facilitate activities in the new area of biomolecular engineering. In order to explore such possibilities, we illustrate four models of biochemical pathways described in our artificial chemistry based on string pattern matching and recombination. The modeled pathways are the replication of DNA, transcription from DNA to mRNA, translation from mRNA to protein, and the oxidation of fatty acids. The descriptions show that the present approach has good modularity and scalability that will be useful for modeling a huge network of pathways. Moreover, we give a procedure to perform reasoning in the artificial chemistry, which checks whether a specified collection of molecules can be generated in a given model, and we demonstrate that it works on a model that describes a natural biochemical pathway. [ABSTRACT FROM AUTHOR]

Purpose. Recent progress suggests that short peptide motifs can be engineered into biopolymers with specific temperature dependent behavior. This review discusses peptide motifs capable of thermo-responsive behavior, and broadly summarizes design approaches that exploit these peptides as drug carriers. This review focuses on one class of thermally responsive peptide-based biopolymers, elastin-like polypeptides in greater detail. Analysis. Four peptide motifs are presented based on leucine zippers, human collagen, human elastin, and silkworm silk that are potential building blocks for thermally responsive biopolymers. When these short motifs (<7 amino acids) are repeated many times, they generate biopolymers with higher order structure and complex temperature triggered behaviors. These structures are thermodynamically modulated, making them intrinsically temperature sensitive. These four motifs can be categorized by the directionality and reversibility of association. Elastin-like polypeptides (ELPs) are one promising motif that reversibly associates during heating. ELPs aggregate sharply above an inverse phase transition temperature, which depends on polymer hydrophobicity, molecular weight, and concentration. ELPs can be modified with chemotherapeutics, are biodegradable, are biocompatible, have low immunogenicity, and have terminal pharmacokinetic half-lives >8 h. ELP block copolymers can reversibly form micelles in response to hyperthermia, and this behavior can modulate the binding avidity of peptide ligands. When high molecular weight ELPs are systemically administered to mice they accumulate in tumors; furthermore, hyperthermia can initiate the ELP phase transition and double the concentration of peptide in the tumor. Conclusions. Temperature sensitive peptides are a powerful engineering platform that will enable new strategies for hyperthermia-directed drug delivery. [ABSTRACT FROM AUTHOR]

Abstract: A review of current processing practices in preparation of recombinant single chain antibody fragments is presented. Single chain antibody fragments which are superior to their Fab and IgG counterparts due to their higher affinity for target antigens while imposing minimal antigenicity in recipient hosts, have sparked breakthroughs in immunology and the medical field at large. The rapidly increasing market demand for pure single chain antibodies for research and therapeutic applications, necessitates viable manufacture routes that can produce large amounts of these antibodies efficiently and as cheaply as possible. Medium- to high-producing expression systems reported for recombinant single chain antibody production are reviewed, and their reported or potential success for efficient commercial-viable preparation of pure antibodies discussed. The effects of expression host system choice on product molecular constraints, ease of processing, and flowsheet design and scale-up are compared. It is concluded that there is no unique host system that can consistently yield high expression levels for a wide range of single chain antibodies; instead, product sequence and end application often dictate the optimum choice of expression host. Irrespective of host systems, adequate a priori design and engineering of the molecular construct supported by good biophysical understanding of the single chain fragment molecules, is a crucial pre-requisite for improved product stability and downstream recovery, which will favourably impact final product yield and functionality. [Copyright &y& Elsevier]

The halogen bond, a noncovalent interaction involving polarizable chlorine, bromine, or iodine molecular substituents, is now being exploited to control the assembly of small molecules in the design of supramolecular complexes and new materials. We demonstrate that a halogen bond formed between a brominated uracil and phosphate oxygen can be engineered to direct the conformation of a biological molecule, in this case to define the conformational isomer of a four-stranded DNA junction when placed in direct competition against a classic hydrogen bond. As a result, this bromine interaction is estimated to be ≈2–5 kcal/mol stronger than the analogous hydrogen bond in this environment, depending on the geometry of the halogen bond. This study helps to establish halogen bonding as a potential tool for the rational design and construction of molecular materials with DNA and other biological macromolecules. [ABSTRACT FROM AUTHOR]

Abstract: With recent advances in biomolecular engineering, the bioremediation of persistent organic pollutants (POPs) using genetically modified microorganisms has become a rapidly growing area of research for environmental protection. Two main biomolecular approaches, rational design and directed evolution, have been developed to engineer enhanced microorganisms and enzymes for the biodegradation of POPs. This review describes the most recent developments and applications of these biomolecular tools for enhancing the capability of microorganisms to bioremediate three major classes of POPs – polycyclic aromatic hydrocabons (PAHs), polychlorinated biphenyls (PCBs) and pesticides. Most of the examples focused on the redesign of various features of the enzymes involved in the bioremediation of POPs, including the enzyme expression level, enzymatic activity and substrate specificity. Overall, the rapidly expanding potential of biomolecular engineering techniques has created the exciting potential of remediating some of the most recalcitrant and hazardous compounds in the environment. [Copyright &y& Elsevier]

Although natural or artificial modified pyrimidine nucleobases represent important molecules with valuable properties as constituents of DNA and RNA, no systematic analyses of the structural aspects of bromo derivatives of cytosine have appeared so far in the literature. In view of the biochemical and pharmaceutical relevance of these compounds, six different crystals containing proton-transfer derivatives of 5-bromocytosine are prepared and analyzed in the solid-state by single crystal X-ray diffraction. All six compounds are organic salts, with proton transfer occurring to the Nimino atom of the pyridine ring. Experimental results are then complemented with Hirshfeld surface analysis to quantitively evaluate the contribution of different intermolecular interactions in the crystal packing. Furthermore, theoretical calculations, based on different arrangements of molecules extracted from the crystal structure determinations, are carried out to analyze the formation mechanism of halogen bonds (XBs) in these compounds and provide insights into the nature and strength of the observed interactions. The results show that the supramolecular architectures of the six molecular salts involve extensive classical intermolecular hydrogen bonds. However, in all but one proton-transfer adducts, weak to moderate XBs are revealed by C–Br...O short contacts between the bromine atom in the fifth position, which acts as XB donor (electron acceptor). Moreover, the lone pair electrons of the oxygen atom of adjacent pyrimidine nucleobases and/or counterions or water molecules, which acts as XB acceptor (electron donor). [ABSTRACT FROM AUTHOR]