Recent metabolomics and gene editing approaches for synthesis of microbial secondary metabolites for drug discovery and development.

Microbial secondary metabolites (SMs) have been identified as an important natural source of drugs for several metabolic and neurological diseases. Along with biomedical applications, SMs are also used in the food and biochemical industries. SMs include natural products such as pigments, alkaloids, toxins, antimicrobials obtained from cultured microorganisms, while other non-cultivable microorganisms have also acted as a rich source of SMs. But, the isolation of SMs from these sources is a very tedious task. Metabolomics provides complete identification and structural information about the entire cellular metabolome under specific conditions using highly sophisticated instrumentation. Further, gene editing techniques such as cloning and gene refactoring, including advanced CRISPR-Cas, can be used for engineering microbes that have the potential to produce natural SMs that were not produced in native microbial strain. The present review describes integrated metabolomics and gene editing approaches for the synthesis of novel microbial SMs and their potential application towards drug discovery and development.

Quest for cardiovascular interventions: precise modeling and 3D printing of heart valves.

Digitalization of health care practices is substantially manifesting itself as an effective tool to diagnose and rectify complex cardiovascular abnormalities. For cardiovascular abnormalities, precise non-invasive imaging interventions are being used to develop patient specific diagnosis and surgical planning. Concurrently, pre surgical 3D simulation and computational modeling are aiding in the effective surgery and understanding of valve biomechanics, respectively. Consequently, 3D printing of patient specific valves that can mimic the original one will become an effective outbreak for valvular problems. Printing of these patient-specific tissues or organ components is becoming a viable option owing to the advances in biomaterials and additive manufacturing techniques. These additive manufacturing techniques are receiving a full-fledged support from burgeoning field of computational fluid dynamics, digital image processing, artificial intelligence, and continuum mechanics during their optimization and implementation. Further, studies at cellular and molecular biomechanics have enriched our understanding of biomechanical factors resulting in valvular heart diseases. Hence, the knowledge generated can guide us during the design and synthesis of biomaterials to develop superior extra cellular matrix, mimicking materials that can be used as a bioink for 3D printing of organs and tissues. With this notion, we have reviewed current opportunities and challenges in the diagnosis and treatment of heart valve abnormalities through patient-specific valve design via tissue engineering and 3D bioprinting. These valves can replace diseased valves by preserving homogeneity and individuality of the patients.

Bioremediation through microbes: systems biology and metabolic engineering approach.

Today, environmental pollution is a serious problem, and bioremediation can play an important role in cleaning contaminated sites. Remediation strategies, such as chemical and physical approaches, are not enough to mitigate pollution problems because of the continuous generation of novel recalcitrant pollutants due to anthropogenic activities. Bioremediation using microbes is an eco-friendly and socially acceptable alternative to conventional remediation approaches. Many microbes with a bioremediation potential have been isolated and characterized but, in many cases, cannot completely degrade the targeted pollutant or are ineffective in situations with mixed wastes. This review envisages advances in systems biology (SB), which enables the analysis of microbial behavior at a community level under different environmental stresses. By applying a SB approach, crucial preliminary information can be obtained for metabolic engineering (ME) of microbes for their enhanced bioremediation capabilities. This review also highlights the integrated SB and ME tools and techniques for bioremediation purposes.

Futuristic biosensors for cardiac health care: an artificial intelligence approach.

Biosensor-based devices are pioneering in the modern biomedical applications and will be the future of cardiac health care. The coupling of artificial intelligence (AI) for cardiac monitoring-based biosensors for the point of care (POC) diagnostics is prominently reviewed here. This review deciphers the most significant machine-learning algorithms for the futuristic biosensors along with the internet of things, computational techniques and microchip-based essential cardiac biomarkers for real-time health monitoring and improving patient compliance. The present review also discusses the recently developed cardiac biosensors along with technical strategies involved in their mechanism of working and their applications in healthcare. Additionally, it provides a key for the ontogeny of an effective and supportive hierarchical protocol for clinical decision-making about personalized medicine through combinatory information analysis, and integrated multidisciplinary AI approaches.

Combinatorial Interactions of Biotic and Abiotic Stresses in Plants and Their Molecular Mechanisms: Systems Biology Approach.

Plants are continually facing biotic and abiotic stresses, and hence, they need to respond and adapt to survive. Plant response during multiple and combined biotic and abiotic stresses is highly complex and varied than the individual stress. These stresses resulted alteration of plant behavior through regulating the levels of microRNA, heat shock proteins, epigenetic variations. These variations can cause many adverse effects on the growth and development of the plant. Further, in natural conditions, several abiotic stresses causing factors make the plant more susceptible to pathogens infections and vice-versa. A very intricate and multifaceted interactions of various biomolecules are involved in metabolic pathways that can direct towards a cross-tolerance and improvement of plant's defence system. Systems biology approach plays a significant role in the investigation of these molecular interactions. The valuable information obtained by systems biology will help to develop stress-resistant plant varieties against multiple stresses. Thus, this review aims to decipher various multilevel interactions at the molecular level under combinatorial biotic and abiotic stresses and the role of systems biology to understand these molecular interactions.

Engineering Thermostable Microbial Xylanases Toward its Industrial Applications.

Xylanases are one of the important hydrolytic enzymes which hydrolyze the ß-1, 4 xylosidic linkage of the backbone of the xylan polymeric chain which consists of xylose subunits. Xylanases are mainly found in plant cell walls and are produced by several kinds of microorganisms such as fungi, bacteria, yeast, and some protozoans. The fungi are considered as most potent xylanase producers than that of yeast and bacteria. There is a broad series of industrial applications for the thermostable xylanase as an industrial enzyme. Thermostable xylanases have been used in a number of industries such as paper and pulp industry, biofuel industry, food and feed industry, textile industry, etc. The present review explores xylanase-substrate interactions using gene-editing tools toward the comprehension in improvement in industrial stability of xylanases. The various protein-engineering and metabolic-engineering methods have also been explored to improve operational stability of xylanase. Thermostable xylanases have also been used for improvement in animal feed nutritional value. Furthermore, they have been used directly in bakery and breweries, including a major use in paper and pulp industry as a biobleaching agent. This present review envisages some of such applications of thermostable xylanases for their bioengineering.

Contemporary enzyme based technologies for bioremediation: A review.

The persistent disposal of xenobiotic compounds like insecticides, pesticides, fertilizers, plastics and other hydrocarbon containing substances is the major source of environmental pollution which needs to be eliminated. Many contemporary remediation methods such as physical, chemical and biological are currently being used, but they are not sufficient to clean the environment. The enzyme based bioremediation is an easy, quick, eco-friendly and socially acceptable approach used for the bioremediation of these recalcitrant xenobiotic compounds from the natural environment. Several microbial enzymes with bioremediation capability have been isolated and characterized from different natural sources, but less production of such enzymes is a limiting their further exploitation. The genetic engineering approach has the potential to get large amount of recombinant enzymes. Along with this, enzyme immobilization techniques can boost the half-life, stability and activity of enzymes at a significant level. Recently, nanozymes may offer the potential bioremediation ability towards a broad range of pollutants. In the present review, we have described a brief overview of the microbial enzymes, different enzymes techniques (genetic engineering and immobilization of enzymes) and nanozymes involved in bioremediation of toxic, carcinogenic and hazardous environmental pollutants.

Strategies to Improve Saccharomyces cerevisiae: Technological Advancements and Evolutionary Engineering.

Bakery industries are thriving to augment the diverse properties of Saccharomyces cerevisiae to increase its flavor, texture and nutritional parameters to attract the more consumers. The improved technologies adopted for quality improvement of baker's yeast are attracting the attention of industry and it is playing a pivotal role in redesigning the quality parameters. Modern yeast strain improvement tactics revolve around the use of several advanced technologies such as evolutionary engineering, systems biology, metabolic engineering, genome editing. The review mainly deals with the technologies for improving S. cerevisiae, with the objective of broadening the range of its industrial applications.

Enhancing the Yield of Active Recombinant Chitobiase by Physico-Chemical and In Vitro Refolding Studies.

Chitobiase (CHB) is an important enzyme for the production of N-acetyl-D-glucosamine from the chitin biopolymer in the series of chitinolytic enzymes. Majority of over-expressed CHB (58%) in E. coli expression system led to formation of inclusion bodies. The production and soluble yield of active CHB was enhanced by co-expression with GroEL/ES chaperonin, optimizing culture conditions and solubilization followed by refolding of remaining inactive chitobiase present in the form of inclusion bodies. The growth of recombinant E. coli produced 42% CHB in soluble form and the rest (~58%) as inclusion bodies. The percentage of active CHB was enhanced to 71% by co-expression with GroEL/ES chaperonin system and optimizing culture conditions (37 °C, 200 rpm, IPTG--0.5 mM, L-arabinose--13.2 mM). Of the remaining inactive CHB present in inclusion bodies, 37% could be recovered in active form using pulsatile dilution method involving denaturants (2 M urea, pH 12.5) and protein refolding studies (1.0 M L-arginine, 5% glycerol). Using combinatorial approach, 80% of the total CHB expressed, could be recovered from cells grown in one litre of LB medium is a step forward in replacing hazardous chemical technology by biotechnological process for the production of NAG from chitinous waste.