生物活性物的生物制造：现状、挑战和发展趋势

生物活性物的生物制造是指利用包括细胞、微生物和酶在内的生物系统生产具有生物活性的天然或合成分子的过程。这些分子可用于制药、化妆品、农业和食品工业等领域,对提高生命质量、延长生命长度具有重要意义。在合成生物学和自动化等技术的推动下,生物制造领域迅速发展,为创造新产品和替代传统产品提供了绿色可持续的生产模式,为生物经济的增长、创新作出了重要贡献。本文结合生物活性物研发及生产情况,简要梳理并分析了国内外生物活性物的现有市场和未来发展。生物制造作为一种绿色、可持续的生产方式,将在生物经济发展中持续发挥重要作用。     

Diagnosis of biofilm infections: current methods used,challenges and perspectives for the future

The diagnosis of biofilms continues to be a challenge, and there is no standardized protocol for such a diagnosis in clinical practice. In addition, some proposed methodologies are expensive to require significant amounts of time and a high number of trained staff, making them impracticable for clinical practice. In recent years, mass spectrophotometry/matrix-assisted laser desorption ionization time of flight (MALDI-TOF) has been applied it in biofilm studies. However, due to several problems and limitations of the technique, MALDI-TOF is far from being the gold standard for identifying biofilm formation. The omics analysis may prove to be a promising strategy for the diagnosis of biofilms in clinical laboratories since it allows the identification of pathogens in less time than needed for conventional techniques and in a more specific manner. However, omic tools are expensive and require qualified technical expertise, and an analysis of the data obtained needs to be careful not to neglect subpopulations in the biofilm. More studies must therefore be developed for creating a protocol that guarantees rapid biofilm identification, ensuring greater chances of success in infection control. This review discusses the current methods of microbial biofilm detection and future perspectives for its diagnosis in clinical practice.     

Feruloyl Esterases as Biotechnological Tools： Current and Future Perspectives

Feruloyl esterases represent a diverse group of hydrolases catalyzing the cleavage and formation of ester bonds between plant cell wall polysaccharide and phenolic acid. They are widely distributed in plants and microorganisms. Besides lipases, a considerable number of microbial feruloyl esterases have also been discovered and overexpressed. This review summarizes the latest research on their classification, production, and biophysicochemical properties. Special emphasis is given to the importance of that type of enzyme and their related phenolic ferulic acid compound in biotechnological processes, and industrial and medicinal applications.     

Properties and biotechnological applications of halohydrin dehalogenases: current state and future perspectives

Halohydrin dehalogenases (HHDHs) are lyases that catalyze the cleavage of carbon–halogen bond of halohydrins. They also can catalyze the reverse reaction in the presence of nucleophiles such as cyanide, azide, and nitrite ions. HHDHs have been recognized as the ideal tools for the degradation of various halogenated environmental pollutants. Moreover, they can be used as biocatalysts for the kinetic resolution of halohydrins and epoxides, and for the preparation of various substituted alcohols. This review is mainly focused on the current status of research on HHDHs, highlighting the production, characterization, structures and mechanism, protein engineering, and biotechnological applications of HHDHs.     

Self-assembled monolayers and polymer brushes in biotechnology: current applications and future perspectives

The chemistry and topography of a surface affect biological response and are of fundamental importance, especially when living systems encounter synthetic surfaces. Most biomolecules have immense recognition power (specific binding) and simultaneously have a tendency to physically adsorb onto a solid substrate without specific receptor recognition (nonspecific adsorption). Therefore, to create useful materials for many biotechnology applications, interfaces are required that have both enhanced specific binding and reduced nonspecific binding. Thus, in applications such as sensors, the tailoring of surface chemistry and the use of micro or nanofabrication techniques becomes an important avenue for the production of surfaces with specific binding properties and minimal background interference. Both self-assembled monolayers (SAMs) and polymer brushes have attracted considerable attention as surface-active materials. In this review, we discuss both of these materials with their potential applications in biotechnology. We also summarize lithographic methods for pattern formation using combined top-down and bottom-up approaches and briefly discuss the future of these materials by describing emerging new applications.     

The diversity,ecology and evolution of extrafloral nectaries: current perspectives and future challenges

Background

Plants in over one hundred families in habitats worldwide bear extrafloral nectaries (EFNs). EFNs display a remarkable diversity of evolutionary origins, as well as diverse morphology and location on the plant. They secrete extrafloral nectar, a carbohydrate-rich food that attracts ants and other arthropods, many of which protect the plant in return. By fostering ecologically important protective mutualisms, EFNs play a significant role in structuring both plant and animal communities. And yet researchers are only now beginning to appreciate their importance and the range of ecological, evolutionary and morphological diversity that EFNs exhibit.

Scope

This Highlight features a series of papers that illustrate some of the newest directions in the study of EFNs. Here, we introduce this set of papers by providing an overview of current understanding and new insights on EFN diversity, ecology and evolution. We highlight major gaps in our current knowledge, and outline future research directions.

Conclusions

Our understanding of the roles EFNs play in plant biology is being revolutionized with the use of new tools from developmental biology and genomics, new modes of analysis allowing hypothesis-testing in large-scale phylogenetic frameworks, and new levels of inquiry extending to community-scale interaction networks. But many central questions remain unanswered; indeed, many have not yet been asked. Thus, the EFN puzzle remains an intriguing challenge for the future.     

Oncoproteomics: current trends and future perspectives

Oncoproteomics is the application of proteomics technologies in oncology. Functional proteomics is a promising technique for the rational identification of biomarkers and novel therapeutic targets for cancers. Recent progress in proteomics has opened new avenues for tumor-associated biomarker discovery. With the advent of new and improved proteomics technologies, such as the development of quantitative proteomic methods, high-resolution, -speed and -sensitivity mass spectrometry and protein arrays, as well as advanced bioinformatics for data handling and interpretation, it is now possible to discover biomarkers that can reliably and accurately predict outcomes during cancer management and treatment. However, there are several difficulties in the study of proteins/peptides that are not inherent in the study of nucleic acids. New challenges arise in large-scale proteomic profiling when dealing with complex biological mixtures. Nevertheless, oncoproteomics offers great promise for unveiling the complex molecular events of tumorigenesis, as well as those that control clinically important tumor behaviors, such as metastasis, invasion and resistance to therapy. In this review, the development and advancement of oncoproteomics technologies for cancer research in recent years are expounded.     

Space biotechnology: current and future perspectives

The potential for obtaining enhanced purities and for achieving greater homogeneity of materials in microgravity first attracted biotechnologists to space bioprocessing. This is but one of the benefits of microgravity. This review discusses the unique opportunities of space biotechnology and the diverse means to achieve microgravity conditions.     

Oncoproteomics: current trends and future perspectives

Oncoproteomics is the application of proteomics technologies in oncology. Functional proteomics is a promising technique for the rational identification of biomarkers and novel therapeutic targets for cancers. Recent progress in proteomics has opened new avenues for tumor-associated biomarker discovery. With the advent of new and improved proteomics technologies, such as the development of quantitative proteomic methods, high-resolution, -speed and -sensitivity mass spectrometry and protein arrays, as well as advanced bioinformatics for data handling and interpretation, it is now possible to discover biomarkers that can reliably and accurately predict outcomes during cancer management and treatment. However, there are several difficulties in the study of proteins/peptides that are not inherent in the study of nucleic acids. New challenges arise in large-scale proteomic profiling when dealing with complex biological mixtures. Nevertheless, oncoproteomics offers great promise for unveiling the complex molecular events of tumorigenesis, as well as those that control clinically important tumor behaviors, such as metastasis, invasion and resistance to therapy. In this review, the development and advancement of oncoproteomics technologies for cancer research in recent years are expounded.     

Super-SILAC: current trends and future perspectives

Stable isotope labeling with amino acids in cell culture (SILAC) has risen as a powerful quantification technique in mass spectrometry (MS)–based proteomics in classical and modified forms. Previously, SILAC was limited to cultured cells because of the requirement of active protein synthesis; however, in recent years, it was expanded to model organisms and tissue samples. Specifically, the super-SILAC technique uses a mixture of SILAC-labeled cells as a spike-in standard for accurate quantification of unlabeled samples, thereby enabling quantification of human tissue samples. Here, we highlight the recent developments in super-SILAC and its application to the study of clinical samples, secretomes, post-translational modifications and organelle proteomes. Finally, we propose super-SILAC as a robust and accurate method that can be commercialized and applied to basic and clinical research.     

A comprehensive benchmark study of multiple sequence alignment methods: current challenges and future perspectives

Multiple comparison or alignmentof protein sequences has become a fundamental tool in many different domains in modern molecular biology, from evolutionary studies to prediction of 2D/3D structure, molecular function and inter-molecular interactions etc. By placing the sequence in the framework of the overall family, multiple alignments can be used to identify conserved features and to highlight differences or specificities. In this paper, we describe a comprehensive evaluation of many of the most popular methods for multiple sequence alignment (MSA), based on a new benchmark test set. The benchmark is designed to represent typical problems encountered when aligning the large protein sequence sets that result from today's high throughput biotechnologies. We show that alignmentmethods have significantly progressed and can now identify most of the shared sequence features that determine the broad molecular function(s) of a protein family, even for divergent sequences. However,we have identified a number of important challenges. First, the locally conserved regions, that reflect functional specificities or that modulate a protein's function in a given cellular context,are less well aligned. Second, motifs in natively disordered regions are often misaligned. Third, the badly predicted or fragmentary protein sequences, which make up a large proportion of today's databases, lead to a significant number of alignment errors. Based on this study, we demonstrate that the existing MSA methods can be exploited in combination to improve alignment accuracy, although novel approaches will still be needed to fully explore the most difficult regions. We then propose knowledge-enabled, dynamic solutions that will hopefully pave the way to enhanced alignment construction and exploitation in future evolutionary systems biology studies.     

Polymers for gene delivery: current status and future perspectives

Gene therapy is a hope for curing many diseases and pathological conditions which are relatively difficult to treat. However lack of proper gene delivery vehicle is the main limiting step in this direction. Though viral vectors still lead as the major vehicle used in gene therapy clinical trials, their immunogenicity and low capacity restrict their wide use. Hence there is a need for developing non-viral vectors which can really be used for clinical applications. Polymers are a versatile group of molecules which can be modified and designed or engineered according to the end needs of the applications. The objective of this review is to summarize the recent advances in the development of polymeric vectors for gene delivery applications reported in patents and scientific journals.     

Cancer metabolism: current perspectives and future directions

Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation'' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles'' heel''. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells.     

Targeted protein degradation: current and future challenges

Traditional approaches in the development of small-molecule drugs typically aim to inhibit the biochemical activity of functional protein domains. In contrast, targeted protein degradation aims to reduce overall levels of disease-relevant proteins. Mechanistically, this can be achieved via chemical ligands that induce molecular proximity between an E3 ubiquitin ligase and a protein of interest, leading to ubiquitination and degradation of the protein of interest. This paradigm-shifting pharmacology promises to address several limitations inherent to conventional inhibitor design. Most notably, targeted protein degradation has the potential not only to expand the druggable proteome beyond the reach of traditional competitive inhibitors but also to develop therapeutic strategies of unmatched selectivity. This review briefly summarizes key challenges that remain to be addressed to deliver on these promises and to realize the full therapeutic potential of pharmacologic modulation of protein degradation pathways.     

Protein-ligand docking: current status and future challenges

Understanding the ruling principles whereby protein receptors recognize, interact, and associate with molecular substrates and inhibitors is of paramount importance in drug discovery efforts. Protein-ligand docking aims to predict and rank the structure(s) arising from the association between a given ligand and a target protein of known 3D structure. Despite the breathtaking advances in the field over the last decades and the widespread application of docking methods, several downsides still exist. In particular, protein flexibility-a critical aspect for a thorough understanding of the principles that guide ligand binding in proteins-is a major hurdle in current protein-ligand docking efforts that needs to be more efficiently accounted for. In this review the key concepts of protein-ligand docking methods are outlined, with major emphasis being given to the general strengths and weaknesses that presently characterize this methodology. Despite the size of the field, the principal types of search algorithms and scoring functions are reviewed and the most popular docking tools are briefly depicted. Recent advances that aim to address some of the traditional limitations associated with molecular docking are also described. A selection of hand-picked examples is used to illustrate these features.     

Cancer pharmacogenomics: current and future applications

Heterogeneity in patient response to chemotherapy is consistently observed across patient populations. Pharmacogenomics is the study of inherited differences in interindividual drug disposition and effects, with the goal of selecting the optimal drug therapy and dosage for each patient. Pharmacogenomics is especially important for oncology, as severe systemic toxicity and unpredictable efficacy are hallmarks of cancer therapies. In addition, genetic polymorphisms in drug metabolizing enzymes and other molecules are responsible for much of the interindividual differences in the efficacy and toxicity of many chemotherapy agents. This review will discuss clinically relevant examples of gene polymorphisms that influence the outcome of cancer therapy, and whole-genome expression studies using microarray technology that have shown tremendous potential for benefiting cancer pharmacogenomics. The power and utility of the mouse as an experimental system for pharmacogenomic discovery will also be discussed in the context of cancer therapy.