Bio-production of lactobionic acid: Current status,applications and future prospects

Lactobionic acid has appeared on the commercial scene as a versatile polyhydroxy acid with numerous promising applications in the food, medicine, pharmaceutical, cosmetics and chemical industries. This high value-added bio-product has recently received growing attention as a bioactive compound, providing an excellent chemical platform for the synthesis of novel potentially biocompatible and biodegradable drug delivery vehicles. Recent advances in tissue engineering and nanomedicine have also underlined the increased importance of this organic acid as a key biofunctionalization agent. The growing commercial relevance of lactobionic acid has therefore prompted the development of novel systems for its biotechnological production that are both sustainable and efficient. The present review explores recent advances and studies related to lactobionic acid bio-production, whether through microbial or enzymatic approaches, highlighting the key bioprocessing conditions for enhanced bio-production. Detailed overviews of the current microbial cell factories as well as downstream processing methodologies for lactobionic acid production are also presented. Furthermore, the potential prospects and current applications of this polyhydroxy acid are also discussed, with an emphasis on the role of lactobionic acid as a key platform in the development of novel drugs, biomaterials, nanoparticles and biopolymer systems.     

Biotechnological production of gluconic acid: future implications

Gluconic acid (GA) is a multifunctional carbonic acid regarded as a bulk chemical in the food, feed, beverage, textile, pharmaceutical, and construction industries. The favored production process is submerged fermentation by Aspergillus niger utilizing glucose as a major carbohydrate source, which accompanied product yield of 98%. However, use of GA and its derivatives is currently restricted because of high prices: about US$ 1.20–8.50/kg. Advancements in biotechnology such as screening of microorganisms, immobilization techniques, and modifications in fermentation process for continuous fermentation, including genetic engineering programmes, could lead to cost-effective production of GA. Among alternative carbohydrate sources, sugarcane molasses, grape must show highest GA yield of 95.8%, and banana must may assist reducing the overall cost of GA production. These methodologies would open new markets and increase applications of GA. Authors’ contributions OVS and RK are the sole contributors of this original review article. This review is based upon the published research in the area of gluconic acid fermentation.     

Deriving metabolic engineering strategies from genome-scale modeling with flux ratio constraints

Optimized production of bio-based fuels and chemicals from microbial cell factories is a central goal of systems metabolic engineering. To achieve this goal, a new computational method of using flux balance analysis with flux ratios (FBrAtio) was further developed in this research and applied to five case studies to evaluate and design metabolic engineering strategies. The approach was implemented using publicly available genome-scale metabolic flux models. Synthetic pathways were added to these models along with flux ratio constraints by FBrAtio to achieve increased (i) cellulose production from Arabidopsis thaliana; (ii) isobutanol production from Saccharomyces cerevisiae; (iii) acetone production from Synechocystis sp. PCC6803; (iv) H₂ production from Escherichia coli MG1655; and (v) isopropanol, butanol, and ethanol (IBE) production from engineered Clostridium acetobutylicum. The FBrAtio approach was applied to each case to simulate a metabolic engineering strategy already implemented experimentally, and flux ratios were continually adjusted to find (i) the end-limit of increased production using the existing strategy, (ii) new potential strategies to increase production, and (iii) the impact of these metabolic engineering strategies on product yield and culture growth. The FBrAtio approach has the potential to design “fine-tuned” metabolic engineering strategies in silico that can be implemented directly with available genomic tools.     

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.     

Biotechnological production of 2,3-butanediol—Current state and prospects

Biotechnological production of 2,3-butanediol (hereafter referred to as 2,3-BD) from wastes and excessive biomass is a promising and attractive alternative for traditional chemical synthesis. In the face of scarcity of fossil fuel supplies the bio-based process is receiving a significant interest, since 2,3-BD may have multiple practical applications (e.g. production of synthetic rubber, plasticizers, fumigants, as an antifreeze agent, fuel additive, octane booster, and many others). Although the 2,3-BD pathway is well known, microorganisms able to ferment biomass to 2,3-BD have been isolated and described, and attempts of pilot scale production of this compound were made, still much has to be done in order to achieve desired profitability. This review summarizes hitherto gained knowledge and experience in biotechnological production of 2,3-BD, sources of biomass used, employed microorganisms both wild type and genetically improved strains, as well as operating conditions applied.     

New application of Bacillus strains for optically pure l-lactic acid production: general overview and future prospects

Members of the genus Bacillus are considered to be both, among the best studied and most commonly used bacteria as well as the most still unexplored and the most wide-applicable potent bacteria because novel Bacillus strains are continuously being isolated and used in various areas. Production of optically pure l-lactic acid (l-LA), a feedstock for bioplastic synthesis, from renewable resources has recently attracted attention as a valuable application of Bacillus strains. l-LA fermentation by other producers, including lactic acid bacteria and Rhizopus strains (fungi) has already been addressed in several reviews. However, despite the advantages of l-LA fermentation by Bacillus strains, including its high growth rate, utilization of various carbon sources, tolerance to high temperature, and growth in simple nutritional conditions, it has not been reviewed. This review article discusses new findings on LA-producing Bacillus strains and compares them to other producers. The future prospects for LA-producing Bacillus strains are also discussed.     

Engineering of microorganisms for the production of biofuels and perspectives based on systems metabolic engineering approaches

The increasing oil price and environmental concerns caused by the use of fossil fuel have renewed our interest in utilizing biomass as a sustainable resource for the production of biofuel. It is however essential to develop high performance microbes that are capable of producing biofuels with very high efficiency in order to compete with the fossil fuel. Recently, the strategies for developing microbial strains by systems metabolic engineering, which can be considered as metabolic engineering integrated with systems biology and synthetic biology, have been developed. Systems metabolic engineering allows successful development of microbes that are capable of producing several different biofuels including bioethanol, biobutanol, alkane, and biodiesel, and even hydrogen. In this review, the approaches employed to develop efficient biofuel producers by metabolic engineering and systems metabolic engineering approaches are reviewed with relevant example cases. It is expected that systems metabolic engineering will be employed as an essential strategy for the development of microbial strains for industrial applications.     

Biotechnological potential of methylotrophic bacteria: a review of current status and future prospects

Major results of the authors' findings on the implementation of biotechnological potential of aerobic methylobacteria and methanotrophs for obtaining forage proteins, biopolymers (polybutyrate and polysaccharides), enzymes (oxidoreductases), and bioprotectors (ectoin), as well as for degrading toxic C1 and Cn compounds have been reviewed. Unique features of the structural and functional organization of the metabolism of extremophilic (tolerant) methylotrophs are discussed, with a view for their prospective use in various fields of modern biotechnology, including biocatalysis and nanotechnology.     

Biotechnological interventions in sea buckthorn (Hippophae L.): current status and future prospects

Sea buckthorn (Hippophae L., Elaeagnaceae) is an economically and ecologically important medicinal plant comprising of species which are winter hardy, dioecious, wind-pollinated multipurpose shrubs bearing yellow or orange berries with nitrogen-fixing ability. It grows widely in cold regions of Indian Himalayas, China, Russia, Europe and many other countries. It is commonly known as ‘cold desert gold’ due to its high potential as a bio-resource for land reclamation, reducing soil erosion and its multifarious uses. The wild populations are being used for harvesting economic benefits with negligible plantation efforts. Although this plant has many excellent traits, it is still in an early phase of domestication. This woody plant is prone to many pests and diseases which destroy the plants and halt its commercial production. Limited progress has been made for improvement of sea buckthorn through breeding programs due to long juvenile period and lack of QTL linkage map, which makes screening of mapping populations a time-consuming and labor-intensive task. Conventional propagation methods, i.e. seeds, softwood and hardwood cuttings, and suckers are in place but are cumbersome and season dependent. Therefore, application of modern tools of biotechnology needs to be standardized for harnessing maximum benefits from this nutraceutical plant. Improvement of this genus through genetic transformation requires an efficient regeneration system, which is yet to be standardized. Taxonomic status of the genus is controversial and requires more inputs. Taxonomic delineation of species and subspecies and also the breeding programs can be more robustly addressed using molecular markers. This review summarizes the progress made and suggests some future directions of research for this important fruit species.     

Laccase applications in biofuels production: current status and future prospects

The desire to reduce dependence on the ever diminishing fossil fuel reserves coupled with the impetus towards green energy has seen increased research in biofuels as alternative sources of energy. Lignocellulose materials are one of the most promising feedstocks for advanced biofuels production. However, their utilisation is dependent on the efficient hydrolysis of polysaccharides, which in part is dependent on cost-effective and benign pretreatment of biomass to remove or modify lignin and release or expose sugars to hydrolytic enzymes. Laccase is one of the enzymes that are being investigated not only for potential use as pretreatment agents in biofuel production, mainly as a delignifying enzyme, but also as a biotechnological tool for removal of inhibitors (mainly phenolic) of subsequent enzymatic processes. The current review discusses the major advances in the application of laccase as a potential pretreatment strategy, the underlying principles as well as directions for future research in the search for better enzyme-based technologies for biofuel production. Future perspectives could include synergy between enzymes that may be required for optimal results and the adoption of the biorefinery concept in line with the move towards the global implementation of the bioeconomy strategy.     

Microbial production of riboflavin: Biotechnological advances and perspectives

Riboflavin is an essential nutrient for humans and animals, and its derivatives flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are cofactors in the cells. Therefore, riboflavin and its derivatives are widely used in the food, pharmaceutical, nutraceutical and cosmetic industries. Advances in biotechnology have led to a complete shift in the commercial production of riboflavin from chemical synthesis to microbial fermentation. In this review, we provide a comprehensive review of biotechnologies that enhance riboflavin production in microorganisms, as well as representative examples. Firstly, the synthesis pathways and metabolic regulatory processes of riboflavin in microorganisms; and the current strategies and methods of metabolic engineering for riboflavin production are systematically summarized and compared. Secondly, the using of systematic metabolic engineering strategies to enhance riboflavin production is discussed, including laboratory evolution, histological analysis and high-throughput screening. Finally, the challenges for efficient microbial production of riboflavin and the strategies to overcome these challenges are prospected.     

Biotechnological production of feed nucleotides by microbial strain improvement

Sodium salts of inosine monophosphate (IMP) and guanosine monophosphate (GMP) are potent flavour enhancers. They are widely used as food additives in combination with monosodium glutamate (MSG) to synergistically increase umami flavour. In recent years, both inosine and guanosine derivatives have gained further importance because of their beneficial effects, related to their antioxidant, neuroprotective, cardiotonic and immunomodulatory properties. The industrial production of both IMP and GMP is mainly achieved either by RNA breakdown and nucleotide extraction or by microbial fermentation using different microorganisms such as Corynebacterium, Bacillus, or Escherichia coli. This work reviews the metabolic pathways and regulatory networks of purine synthesis, including both IMP and GMP, and the biotechnological processes applied to the production of these compounds, ranging from classical random mutagenesis to rational design by metabolic engineering. Recent advances of systems biology approaches, along with the rapid development of synthetic biology, may offer a basis for future manipulations to further increase the productivity of the fermentation processes.     

蓝细菌乙醇光合细胞工厂的发展与展望

生物乙醇是极具应用潜力和代表性的生物能源产品之一。以蓝细菌为光合平台,利用二氧化碳和太阳能直接进行乙醇合成可以同时起到降低二氧化碳排放和提供可再生能源的效果,具有重要的研究与应用价值。本文回顾了蓝细菌乙醇光合细胞工厂相关技术的发展历程和现状,从途径优化、底盘选择和代谢工程策略等层面对其最新进展和所遇到的问题进行了总结介绍,并对该技术未来发展方向进行了展望。     

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.     

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.     

Biotechnological production and application of vitamin E: current state and prospects

Tocochromanols (tocopherols and tocotrienols) are important lipophilic antioxidants for animals and humans. Their biological activity is expressed as vitamin E activity. This article describes the current need for vitamin E production, and compares different strategies to engineer the vitamin E content in photosynthetic bacteria and plants, with a focus on oilseed as target tissues. The current status of biotechnological advances in tocochromanol pathway engineering is summarized, and current limitations in our understanding of the tocochromanol biosynthetic pathway are discussed.