Journal: Biotechnology advances
Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a “screening hit” through a “drug lead” to a “marketed drug” is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.
Interest in thermophilic bacteria as live-cell catalysts in biofuel and biochemical industry has surged in recent years, due to their tolerance of high temperature and wide spectrum of carbon-sources that include cellulose. However their direct employment as microbial cellular factories in the highly demanding industrial conditions has been hindered by uncompetitive biofuel productivity, relatively low tolerance to solvent and osmic stresses, and limitation in genome engineering tools. In this work we review recent advances in dissecting and engineering the metabolic and regulatory networks of thermophilic bacteria for improving the traits of key interest in biofuel industry: cellulose degradation, pentose-hexose co-utilization, and tolerance of thermal, osmotic, and solvent stresses. Moreover, new technologies enabling more efficient genetic engineering of thermophiles were discussed, such as improved electroporation, ultrasound-mediated DNA delivery, as well as thermo-stable plasmids and functional selection systems. Expanded applications of such technological advancements in thermophilic microbes promise to substantiate a synthetic biology perspective, where functional parts, module, chassis, cells and consortia were modularly designed and rationally assembled for the many missions at industry and nature that demand the extraordinary talents of these extremophiles.
Cellulose acetate (CA) has been a material of choice for spectrum of utilities across different domains ranging from high absorbing diapers to membrane filters. Electrospinning has conferred a whole new perspective to polymeric materials including CA in the context of multifarious applications across myriad of niches. In the present review, we try to bring out the recent trend (focussed over last five years' progress) of research on electrospun CA fibers of nanoscale regime in the context of developmental strategies of their blends and nanocomposites for advanced applications. In the realm of biotechnology, electrospun CA fibers have found applications in biomolecule immobilization, tissue engineering, bio-sensing, nutraceutical delivery, bioseparation, crop protection, bioremediation and in the development of anti-counterfeiting and pH sensitive material, photocatalytic self-cleaning textile, temperature-adaptable fabric, and antimicrobial mats, amongst others. The present review discusses these diverse applications of electrospun CA nanofibers.
Arundo donax L., common name giant cane or giant reed, is a plant that grows spontaneously in different kinds of environments and that it is widespread in temperate and hot areas all over the world. Plant adaptability to different kinds of environment, soils and growing conditions, in combination with the high biomass production and the low input required for its cultivation, give to A. donax many advantages when compared to other energy crops. A. donax can be used in the production of biofuels/bioenergy not only by biological fermentation, i.e. biogas and bio-ethanol, but also, by direct biomass combustion. Both its industrial uses and the extraction of chemical compounds are largely proved, so that A. donax can be proposed as the feedstock to develop a bio-refinery. Nowadays, the use of this non-food plant in both biofuel/bioenergy and bio-based compound production is just beginning, with great possibilities for expanding its cultivation in the future. To this end, this review highlights the potential of using A. donax for energy and bio-compound production, by collecting and critically discussing the data available on these first applications for the crop.
Alzheimer’s disease (AD) is a severe, chronic and progressive neurodegenerative disease associated with memory and cognition impairment ultimately leading to death. It is the commonest reason of dementia in elderly populations mostly affecting beyond the age of 65. The pathogenesis is indicated by accumulation of the amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFT) in brain tissues and hyperphosphorylation of tau protein in neurons. The main cause is considered to be the formation of reactive oxygen species (ROS) due to oxidative stress. The current treatment provides only symptomatic relief by offering temporary palliative therapy which declines the rate of cognitive impairment associated with AD. Inhibition of the enzyme acetylcholinesterase (AChE) is considered as one of the major therapeutic strategies offering only symptomatic relief and moderate disease-modifying effect. Other non-cholinergic therapeutic approaches include antioxidant and vitamin therapy, stem cell therapy, hormonal therapy, use of antihypertensive or lipid-lowering medications and selective phosphodiesterase (PDE) inhibitors, inhibition of β-secretase and γ-secretase and Aβ aggregation, inhibition of tau hyperphosphorylation and intracellular NFT, use of nonsteroidal anti-inflammatory drugs (NSAIDs), transition metal chelators, insulin resistance drugs, etanercept, brain-derived neurotrophic factor (BDNF) etc. Medicinal plants have been reported for possible anti-AD activity in a number of preclinical and clinical trials. Ethnobotany, being popular in China and in the Far East and possibly less emphasized in Europe, plays a substantial role in the discovery of anti-AD agents from botanicals. Chinese Material Medica (CMM) involving Chinese medicinal plants has been used traditionally in China in the treatment of AD. Ayurveda has already provided numerous lead compounds in drug discovery and many of these are also undergoing clinical investigations. A number of medicinal plants either in their crude forms or as isolated compounds have exhibited to reduce the pathological features associated with AD. In this present review, an attempt has been made to elucidate the molecular mode of action of various plant extracts, phytochemicals and traditional herbal formulations investigated against AD as reported in various preclinical and clinical tests. Herbal synergism often found in polyherbal formulations were found effective to combat disease heterogeneity as found in complex pathogenesis of AD. Finally a note has been added to describe biotechnological improvement, genetic and genomic resources and mathematical and statistical techniques for empirical model building associated with anti-AD plant secondary metabolites and their source botanicals.
Aerobic granular sludge technology has been extensively studied over the past 20 years and is regarded as the upcoming new standard for biological treatment of domestic and industrial wastewaters. Aerobic granules (AG) are dense, compact, self-immobilized microbial aggregates that allow better sludge-water separation and thereby higher biomass concentrations in the bioreactor than conventional activated sludge aggregates. This brings potential practical advantages in terms of investment cost, energy consumption and footprint. Yet, despite the relevant advances regarding the process of AG formation, instability of AG during long-term operation is still seen as a major barrier for a broad practical application of this technology. This paper presents an up-to-date review of the literature focusing on AG stability, aiming to contribute to the identification of key factors for promoting long-term stability of AG and to a better understanding of the underlying mechanisms. Operational conditions leading to AG disintegration are described, including high organic loads, particulate substrates in the influent, toxic feed components, aerobic feeding and too short famine periods. These operational and influent wastewater composition conditions were shown to influence the micro-environment of AG, consequently affecting their stability. Granule stability is generally favored by the presence of a dense core, with microbial growth throughout the AG depth being a crucial intrinsic factor determining its structural integrity. Accordingly, possible practical solutions to improve granule long-term stability are described, namely through the promotion of minimal substrate concentration gradients and control of microbial growth rates within AG, including anaerobic, plug-flow feeding and specific sludge removal strategies.
The anticancer effects of polyphenols are ascribed to several signaling pathways including the tumor suppressor gene tumor protein 53 (p53). Expression of endogenous p53 is silent in various types of cancers. A number of polyphenols from a wide variety of dietary sources could upregulate p53 expression in several cancer cell lines through distinct mechanisms of action. The aim of this review is to focus the significance of p53 signaling pathways and to provide molecular intuitions of dietary polyphenols in chemoprevention by monitoring p53 expression that have a prominent role in tumor suppression.
The development of customizable sequence-specific nucleases such as TALENs, ZFNs and the powerful CRISPR/Cas9 system has revolutionized the field of genome editing. The CRISPR/Cas9 system is particularly versatile and has been applied in numerous species representing all branches of life. Regardless of the target organism, all researchers using sequence-specific nucleases face similar challenges: confirmation of the desired on-target mutation and the detection of off-target events. Here, we evaluate the most widely-used methods for the detection of on-target and off-target mutations in terms of workflow, sensitivity, strengths and weaknesses.
Pseudomonas aeruginosa is an opportunistic pathogen that is a leading cause of morbidity and mortality in cystic fibrosis patients and immunocompromised individuals. Eradication of P. aeruginosa has become increasingly difficult due to its remarkable capacity to resist antibiotics. Strains of Pseudomonas aeruginosa are known to utilize their high levels of intrinsic and acquired resistance mechanisms to counter most antibiotics. In addition, adaptive antibiotic resistance of P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant persister cells, and is responsible for recalcitrance and relapse of infections. The discovery and development of alternative therapeutic strategies that present novel avenues against P. aeruginosa infections are increasingly demanded and gaining more and more attention. Although mostly at the preclinical stages, many recent studies have reported several innovative therapeutic technologies that have demonstrated pronounced effectiveness in fighting against drug-resistant P. aeruginosa strains. This review highlights the mechanisms of antibiotic resistance in P. aeruginosa and discusses the current state of some novel therapeutic approaches for treatment of P. aeruginosa infections that can be further explored in clinical practice.
The non-conventional oleaginous yeast Yarrowia lipolytica shows great industrial promise. It naturally produces certain compounds of interest but can also artificially generate non-native metabolites, thanks to an engineering process made possible by the significant expansion of a dedicated genetic toolbox. In this review, we present recently developed synthetic biology tools that facilitate the manipulation of Y. lipolytica, including 1) DNA assembly techniques, 2) DNA parts for constructing expression cassettes, 3) genome-editing techniques, and 4) computational tools.