Biotechnological production of muconic acid: current status and future prospects

Muconic acid (MA), a high value-added bio-product with reactive dicarboxylic groups and conjugated double bonds, has garnered increasing interest owing to its potential applications in the manufacture of new functional resins, bio-plastics, food additives, agrochemicals, and pharmaceuticals. At the very least, MA can be used to produce commercially important bulk chemicals such as adipic acid, terephthalic acid and trimellitic acid. Recently, great progress has been made in the development of biotechnological routes for MA production. This present review provides a comprehensive and systematic overview of recent advances and challenges in biotechnological production of MA. Various biological methods are summarized and compared, and their constraints and possible solutions are also described. Finally, the future prospects are discussed with respect to the current state, challenges, and trends in this field, and the guidelines to develop high-performance microbial cell factories are also proposed for the MA production by systems metabolic engineering.     

Coenzyme Q10 production in plants: current status and future prospects

Coenzyme Q10 (CoQ10) or Ubiquinone10 (UQ10), an isoprenylated benzoquinone, is well-known for its role as an electron carrier in aerobic respiration. It is a sole representative of lipid soluble antioxidant that is synthesized in our body. In recent years, it has been found to be associated with a range of patho-physiological conditions and its oral administration has also reported to be of therapeutic value in a wide spectrum of chronic diseases. Additionally, as an antioxidant, it has been widely used as an ingredient in dietary supplements, neutraceuticals, and functional foods as well as in anti-aging creams. Since its limited dietary uptake and decrease in its endogenous synthesis in the body with age and under various diseases states warrants its adequate supply from an external source. To meet its growing demand for pharmaceutical, cosmetic and food industries, there is a great interest in the commercial production of CoQ10. Various synthetic and fermentation of microbial natural producers and their mutated strains have been developed for its commercial production. Although, microbial production is the major industrial source of CoQ10 but due to low yield and high production cost, other cost-effective and alternative sources need to be explored. Plants, being photosynthetic, producing high biomass and the engineering of pathways for producing CoQ10 directly in food crops will eliminate the additional step for purification and thus could be used as an ideal and cost-effective alternative to chemical synthesis and microbial production of CoQ10. A better understanding of CoQ10 biosynthetic enzymes and their regulation in model systems like E. coli and yeast has led to the use of metabolic engineering to enhance CoQ10 production not only in microbes but also in plants. The plant-based CoQ10 production has emerged as a cost-effective and environment-friendly approach capable of supplying CoQ10 in ample amounts. The current strategies, progress and constraints of CoQ10 production in plants are discussed in this review.     

Cacao biotechnology: current status and future prospects

Theobroma cacao—The Food of the Gods, provides the raw material for the multibillion dollar chocolate industry and is also the main source of income for about 6 million smallholders around the world. Additionally, cocoa beans have a number of other nonfood uses in the pharmaceutical and cosmetic industries. Specifically, the potential health benefits of cocoa have received increasing attention as it is rich in polyphenols, particularly flavonoids. At present, the demand for cocoa and cocoa‐based products in Asia is growing particularly rapidly and chocolate manufacturers are increasing investment in this region. However, in many Asian countries, cocoa production is hampered due to many reasons including technological, political and socio‐economic issues. This review provides an overview of the present status of global cocoa production and recent advances in biotechnological applications for cacao improvement, with special emphasis on genetics/genomics, in vitro embryogenesis and genetic transformation. In addition, in order to obtain an insight into the latest innovations in the commercial sector, a survey was conducted on granted patents relating to T. cacao biotechnology.     

Energy crops: current status and future prospects

Energy crops currently contribute a relatively small proportion to the total energy produced from biomass each year, but the proportion is set to grow over the next few decades. This paper reviews the current status of energy crops and their conversion technologies, assesses their potential to contribute to global energy demand and climate mitigation over the next few decades, and examines the future prospects. Previous estimates have suggested a technical potential for energy crops of～400 EJ yr^?1 by 2050. In a new analysis based on energy crop areas for each of the IPCC SRES scenarios in 2025 (as projected by the IMAGE 2.2 integrated assessment model), more conservative dry matter and energy yield estimates and an assessment of the impact on non‐CO₂ greenhouse gases were used to estimate the realistically achievable potential for energy crops by 2025 to be between 2 and 22 EJ yr^?1, which will offset～100–2070 Mt CO₂‐eq. yr^?1. These results suggest that additional production of energy crops alone is not sufficient to reduce emissions to meet a 550 μmol mol^?1 atmospheric CO₂ stabilization trajectory, but is sufficient to form an important component in a portfolio of climate mitigation measures, as well as to provide a significant sustainable energy resource to displace fossil fuel resources. Realizing the potential of energy crops will necessitate optimizing the dry matter and energy yield of these crops per area of land through the latest biotechnological routes, with or without the need for genetic modification. In future, the co‐benefits of bioenergy production will need to be optimized and methods will need to be developed to extract and refine high‐value products from the feedstock before it is used for energy production.     

Vitamin K series: current status and future prospects

The Vitamin K series, particularly menaquinone, have been attracting research attention, due to the potential in reducing both osteoporosis and cardiovascular diseases. This review provides an overview of the types of vitamin K and their health benefits. This is followed by a critical review of the various biotechnological approaches used in the production of menaquinone, including solid and liquid state fermentations, extraction and recovery. The currently available market information is summarized and future growth prospects are discussed. Recommendations are also given for areas of future research in order to improve the production process for menaquinone and reduce costs.     

The nitrile-degrading enzymes: current status and future prospects

Nitrile-converting enzymes are becoming commonplace in the synthesis of pharmaceuticals and commodity chemicals. These versatile biocatalysts have potential applications in different fields including synthetic biocatalysis and bioremediation. This review attempts to describe in detail the three major classes of nitrile-converting enzymes, namely nitrilases, nitrile hydratases and amidases. Various aspects of these enzymes including their occurrence, mechanism of action, characteristics and applicability in different sectors have been elaborately elucidated. Cloning of genes related to nitrile-converting enzymes is also discussed.     

Nitrogen assimilation in plants: current status and future prospects

Nitrogen(N) is the driving force for crop yields; however, excessive N application in agriculture not only increases production cost, but also causes severe environmental problems. Therefore, comprehensively understanding the molecular mechanisms of N use efficiency(NUE) and breeding crops with higher NUE is essential to tackle these problems. NUE of crops is determined by N uptake, transport, assimilation, and remobilization. In the process of N assimilation, nitrate reductase(NR), nitrite redu...     

Functional markers in wheat: current status and future prospects

Functional markers (FM) are developed from sequence polymorphisms present in allelic variants of a functional gene at a locus. FMs accurately discriminate alleles of a targeted gene, and are ideal molecular markers for marker-assisted selection in wheat breeding. In this paper, we summarize FMs developed and used in common wheat. To date, more than 30 wheat loci associated with processing quality, agronomic traits, and disease resistance, have been cloned, and 97 FMs were developed to identify 93 alleles based on the sequences of those genes. A general approach is described for isolation of wheat genes and development of FMs based on in silico cloning and comparative genomics. The divergence of DNA sequences of different alleles that affect gene function is summarized. In addition, 14 molecular markers specific for alien genes introduced from common wheat relatives were also described. This paper provides updated information on all FMs and gene-specific STS markers developed so far in wheat and should facilitate their application in wheat breeding programs.     

Multidimensional protein identification technology: current status and future prospects

Protein profiling using high-throughput tandem mass spectrometry has become a powerful method for analyzing changes in global protein expression patterns in cells and tissues as a function of developmental, physiologic and disease processes. This review summarizes the utility and practical application of multidimensional protein identification technology as a platform for comprehensive proteomic profiling of complex biologic samples. The strengths and potential problems and limitations associated with this powerful technology are discussed, with an emphasis placed on one of the biggest challenges currently facing large-scale expression profiling projects -- namely, data analysis. Complementary bioinformatic computational data mining strategies, such as clustering, functional annotation and statistical inference, are also discussed as these are increasingly necessary for interpreting the results of global proteomic profiling studies.     

Genetic transformation of wheat: current status and future prospects

Genetic transformation is a reverse genetics tool for validation of target genes and crop improvement. However, due to its low efficiency and genotype dependency, wheat is considered a recalcitrant plant for genetic transformation. During the last 20 years, various in vitro and in planta transformation methods have been reported in wheat. Until now, biolistic particle and Agrobacterium-mediated wheat transformation methods using immature embryos as explants have been the two major transformation approaches. In addition to immature embryos, other explant types, such as mature embryos, anther-derived calli, inflorescences, apical meristems, and other floral organs, have been employed; however, they need further optimization. In addition to the common marker genes, such as bar, hpt and gus, other effective markers, ALS, AtMYB12 and pmi, have been successfully used for selection of positive transgenic plants. Numerous agronomic trait genes such as biotic stress resistance or tolerance genes have been transferred into wheat plants. Future prospects, such as recipient wheat cultivars and explants, marker free issues, and transgene silencing, are discussed. The objective of this review is to summarize current successful techniques for wheat transformation and stimulate further research into long-term wheat improvement by genetic engineering approaches.     

Molecular basis of obesity: current status and future prospects

Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of "deep phenotyping" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.     

Genetic engineering of millets: current status and future prospects

This review summarizes progress on the genetic transformation of millets and discusses the future prospects for the development of improved varieties. Only a limited number of studies have been carried out on genetic improvement of millets despite their nutritional importance in supplying minerals, calories and protein. Most genetic transformation studies of millets have been restricted to pearl millet and bahiagrass and most studies have been limited to the assessment of reporter and marker gene expression. Biolistic-mediated gene delivery has been frequently used for the transformation of millets but Agrobacterium-mediated transformation is still lagging. Improved transformation of millets, allied to relevant gene targets which may offer, for example, improved nutritional quality, resistance to abiotic and biotic stresses, and resistance to fungal infection will play important roles in millet improvement.     

Antenatal genetic diagnosis: current status and future prospects.

The current status of antenatal genetic diagnosis is reviewed and the limitations of present techniques are discussed. It is suggested that multidisciplinary clinics are the most efficient means of providing this aspect of health care. Advances in cell culture techniques, in ultrasonography and in fetoscopy will extend the services available, and the impact of this will be felt by the community. Education of the medical profession and the public in this area is necessary so that informed decision-making can take place.     

Multidimensional protein identification technology: current status and future prospects

Protein profiling using high-throughput tandem mass spectrometry has become a powerful method for analyzing changes in global protein expression patterns in cells and tissues as a function of developmental, physiologic and disease processes. This review summarizes the utility and practical application of multidimensional protein identification technology as a platform for comprehensive proteomic profiling of complex biologic samples. The strengths and potential problems and limitations associated with this powerful technology are discussed, with an emphasis placed on one of the biggest challenges currently facing large-scale expression profiling projects – namely, data analysis. Complementary bioinformatic computational data mining strategies, such as clustering, functional annotation and statistical inference, are also discussed as these are increasingly necessary for interpreting the results of global proteomic profiling studies.     

Management of COVID-19: current status and future prospects

COVID-19, a highly transmissible pandemic disease, is affecting millions of lives around the world. Severely infected patients show acute respiratory distress symptoms. Sustainable management strategies are required to save lives of the infected people and further preventing spread of the virus. Diagnosis, treatment, and vaccination development initiatives are already exhibited from the scientific community to fight against this virus. In this review, we primarily discuss the management strategies including prevention of spread, prophylaxis, vaccinations, and treatment for COVID-19. Further, analysis of vaccine development status and performance are also briefly discussed. Global socioeconomic impact of COVID-19 is also analyzed as part of this review.     

Mesenchymal stem cells and immunomodulation: current status and future prospects

The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application. An understanding of the biological properties of MSCs will clarify the mechanisms of MSC-based transplantation for immunomodulation. In this review, we summarize the preclinical and clinical studies of MSCs from different adult tissues, discuss the current hurdles to their use and propose the future development of pluripotent stem cell-derived MSCs as an approach to immunomodulation therapy.     

Anti-angiogenic gene therapy of cancer: current status and future prospects

The discovery of endogenous inhibitors of angiogenesis has made it possible to test the hypothesis that blocking the angiogenic switch may keep tumor growth in check, and has added a new investigational arm to the field of cancer gene therapy. Angiogenesis inhibitors are heterogeneous in origin and potency, and their growing list includes proteolysis products of larger molecules with a different function, such as angiostatin, endostatin and vasostatin, modulators of vascular endothelial growth factor activity, such as sFLT-1, and some cytokines/chemokines with marked anti-endothelial activity, such as IL-12, IFN-alpha, and CXCL10. Pre-clinical studies have clearly indicated that these factors are essentially cytostatic and that they need long-term administration in order to obtain prolonged anti-tumor effects, representing a rational basis for their delivery by a gene therapy approach. The experimental approaches attempted to date, reviewed herein, indicate overall that anti-angiogenic gene therapy has efficacy mainly as an early intervention strategy and that a better understanding of the biological mechanisms underlying resistance to angiogenesis inhibition, as well as appropriate combined treatments, are required to generate a conceptual advancement which could drive the field towards successful management of established tumors.