Current studies on the enzymatic preparation 2-O-α-d-glucopyranosyl-l-ascorbic acid with cyclodextrin glycosyltransferase

2-O-α-d-glucopyranosyl-l-ascorbic acid (AA-2G) is one of the most important l-ascorbic acid derivatives because of its resistance to reduction and oxidation and its easy degradation by α-glucosidase to release l-ascorbic acid and glucose. Thus, AA-2G has commercial uses in food, medicines and cosmetics. This article presents a review of recent studies on the enzymatic production of AA-2G using cyclodextrin glycosyltransferase. Reaction mechanisms with different donor substrates are discussed. Protein engineering, physical and biological studies of cyclodextrin glycosyltransferase are introduced from the viewpoint of effective AA-2G production. Future prospects for the production of AA-2G using cyclodextrin glycosyltransferase are reviewed.     

Biotechnological production of <Emphasis Type="SmallCaps">d</Emphasis>-glyceric acid and its application

Glycerol is currently produced in large amounts as a by-product during fat splitting and biodiesel fuel production. Over the past decade, both chemical and biotechnological processes to convert glycerol to value-added chemicals have been increasingly explored. This mini-review provides recent information about the biotechnological production of a glycerol derivative, d-glyceric acid (d-GA), and its possible applications. Little is known about GA as a bioproduct, but it is naturally found in different kinds of plants as a phytochemical constituent and is reported to have some biological activity. A racemic mixture of dl-GA can be obtained from glycerol via chemical oxidation; however, d-GA is mainly biotechnologically produced with the aid of bacteria. Under aerobic conditions, some acetic acid bacteria transform glycerol into d-GA, and optimization of initial glycerol concentration and aeration rate provided a yield of more than 80 g/l d-GA, using a strain of Gluconobacter frateurii.     

Hyaluronic acid: separation and biological implications

Hyaluronic acid (hyaluronan) is a ubiquitous extracellular matrix component, and present at high concentrations in skin, joints and cornea. In the skin, it is synthesized primarily by dermal fibroblasts and by epidermal keratinocytes. Hyaluronic acid usually exists as a high molecular mass (600,000-1,000,000) and non-sulfated glycosaminoglycan composed of a disaccharide unit of [bond]3GlcNAc beta 1[bond]4GlcA beta 1[bond]. Hyaluronic acid has been widely used not only for osteoarthritis and ophthalmology but also for cosmetics for skin care. To examine the biological activities of hyaluronic acid, we have to accurately determine the quantity and molecular masses in biological samples. We review recent development in the analysis of hyaluronic acid having various molecular sizes using electrophoretic and chromatographic techniques. Recently, interactions between hyaluronic acid oligomers and hyaluronic acid-binding proteins have attracted the interest for understanding the biological functions. We show some interesting reports on biological interactions of hyaluronic acid and its oligomers with some proteins.     

Production of lactic acid from renewable materials by Rhizopus fungi

Lactic acid is a commonly occurring organic acid, which is valuable due to its wide use in food and food-related industries, and its potential for the production of biodegradable and biocompatible polylactate polymers. Lactic acid can be produced from renewable materials using various fungal species of the Rhizopus genus, which have advantages compared to the bacteria, including their amylolytic characteristics, low nutrient requirements and valuable fermentation by-product—fungal biomass. This paper reviews recent research in process engineering, metabolic and enzymetic mechanisms, and molecular biotechnology associated with lactic acid production by the Rhizopus fungi to get a better understanding of biochemical activities. The major process components: renewable materials, bioreactor systems and process modeling are reviewed. The role of key bioprocess parameters, such as nutrient composition, pH and growth morphology, involved in the production of lactic acid is discussed in detail. In addition, recent advances in simultaneous saccharification and fermentation, molecular genetic approaches, and enzymetic and metabolic pathways involved in the production of lactic acid by fungal strains are discussed.     

Versatile roles of plant NADPH oxidases and emerging concepts

NADPH oxidase (NOX) is a key player in the network of reactive oxygen species (ROS) producing enzymes. It catalyzes the production of superoxide (O₂⁻), that in turn regulates a wide range of biological functions in a broad range of organisms. Plant Noxes are known as respiratory burst oxidase homologs (Rbohs) and are homologs of catalytic subunit of mammalian phagocyte gp91^phox. They are unique among other ROS producing mechanisms in plants as they integrate different signal transduction pathways in plants. In recent years, there has been addition of knowledge on various aspects related to its structure, regulatory components and associated mechanisms, and its plethora of biological functions. This update highlights some of the recent developments in the field with particular reference to important members of the plant kingdom.     

New trends in biotechnological production of rosmarinic acid

Rosmarinic acid (RA), an ester of caffeic acid and 3,4-dihydroxyphenyl lactic acid, is widely distributed in the plant kingdom. Interest in it is growing due to its promising biological activities, including cognitive-enhancing effects and slowing the development of Alzheimer’s disease, cancer chemoprotection or anti-inflammatory activity, among others. In order to meet the increasing demand for this compound, several biotechnological approaches to its production based on plant cell and hairy root cultures have been developed. Empirical strategies are currently being combined with metabolic engineering tools to increase RA production in plant cell platforms in a more rational way. Discussed here are the latest advances in the field, together with recent trends in plant biotechnology, such as the application of single use technology and the use of biosensors in downstream processes.     

酶法生产共轭亚油酸的研究进展

共轭亚油酸(Conjugated linoleic acid,CLA)具有抗癌、抗动脉粥样硬化、减肥和免疫调节等生理活性。共轭亚油酸可以通过酶法异构化获得,将底物亚油酸异构形成具有生物活性物质-共轭亚油酸的异构酶称为亚油酸异构酶。因此,通过介绍亚油酸异构酶的来源、作用机制、酶学性质和基因工程菌生产等方面的研究进展,结合不断发展的基因工程技术,旨在提高亚油酸异构酶的活性、产量和异构化效率,以扩大反应底物范围,降低生产成本,从而推进共轭亚油酸的规模化、可持续性的工业生产。     

Biological roles of lysophosphatidic acid signaling through its production by autotaxin

Lysophosphatidic acid (LPA) exhibits a wide variety of biological functions as a bio-active lysophospholipid through G-protein-coupled receptors specific to LPA. Currently at least six LPA receptors are identified, named LPA₁ to LPA₆, while the existence of other LPA receptors has been suggested. From studies on knockout mice and hereditary diseases of these LPA receptors, it is now clear that LPA is involved in various biological processes including brain development and embryo implantation, as well as patho-physiological conditions including neuropathic pain and pulmonary and renal fibrosis. Unlike sphingosine 1-phosphate, a structurally similar bio-active lysophospholipid to LPA and produced intracellularly, LPA is produced by multiple extracellular degradative routes. A plasma enzyme called autotaxin (ATX) is responsible for the most of LPA production in our bodies. ATX converts lysophospholipids such as lysophosphatidylcholine to LPA by its lysophospholipase D activity. Recent studies on ATX have revealed new aspects of LPA. In this review, we highlight recent advances in our understanding of LPA functions and several aspects of ATX, including its activity, expression, structure, biochemical properties, the mechanism by which it stimulates cell motility and its pahto-physiological function through LPA production.     

Biotechnological processes for biodiesel production using alternative oils

As biodiesel (fatty acid methyl ester (FAME)) is mainly produced from edible vegetable oils, crop soils are used for its production, increasing deforestation and producing a fuel more expensive than diesel. The use of waste lipids such as waste frying oils, waste fats, and soapstock has been proposed as low-cost alternative feedstocks. Non-edible oils such as jatropha, pongamia, and rubber seed oil are also economically attractive. In addition, microalgae, bacteria, yeast, and fungi with 20% or higher lipid content are oleaginous microorganisms known as single cell oil and have been proposed as feedstocks for FAME production. Alternative feedstocks are characterized by their elevated acid value due to the high level of free fatty acid (FFA) content, causing undesirable saponification reactions when an alkaline catalyst is used in the transesterification reaction. The production of soap consumes the conventional catalyst, diminishing FAME production yield and simultaneously preventing the effective separation of the produced FAME from the glycerin phase. These problems could be solved using biological catalysts, such as lipases or whole-cell catalysts, avoiding soap production as the FFAs are esterified to FAME. In addition, by-product glycerol can be easily recovered, and the purification of FAME is simplified using biological catalysts.     

Biosynthesis of lactate-containing polyesters by metabolically engineered bacteria

Due to increasing concerns about environmental problems, climate change and limited fossil resources, bio-based production of chemicals and polymers is gaining attention as one of the solutions to these problems. Polyhydroxyalkanoates (PHAs) are polyesters that can be produced by microbial fermentation. PHAs are synthesized using monomer precursors provided from diverse metabolic pathways and are accumulated as distinct granules inside the cells. On the other hand, most so-called bio-based polymers including polybutylene succinate, polytrimethylene terephthalate, and polylactic acid (PLA) are synthesized by a chemical process using monomers produced by fermentation. PLA, an attractive biomass-derived plastic, is currently synthesized by heavy metal-catalyzed ring opening polymerization of L-lactide that is made from fermentation-derived L-lactic acid. Recently, a complete biological process for the production of PLA and PLA copolymers from renewable resources has been developed by direct fermentation of recombinant bacteria employing PHA biosynthetic pathways coupled with a novel metabolic pathway. This could be accomplished by establishing a pathway for generating lactyl-CoA and engineering PHA synthase to accept lactyl-CoA as a substrate combined with systems metabolic engineering. In this article, we review recent advances in the production of lactate-containing homo- and co-polyesters. Challenges remaining to efficiently produce PLA and its copolymers and strategies to overcome these challenges through metabolic engineering combined with enzyme engineering are discussed.     

The role of parasitoid and predator production in technology transfer of field crop biological control

The immediate goals for improving natural enemy production are to reduce costs, increase efficacy and provide additional species for pest management. This paper describes expanding markets for natural enemies that are or could be produced commercially, gives operational and experimental examples of parasitoid and predator production for use in field crop biological control, defines some of the obstacles and makes recommendations for producing and using natural enemies. Additionally, it provides recent published guidance for implementing biological control in Integrated Pest Management.     

Biological activity of usnic acid and its derivatives: Part 1. Activity against unicellular organisms

Usnic acid (UA) is a commercially available lichen metabolite. Its biological activity is diverse. Its broad occurrence in various lichen species, simple isolation procedure, and high optical purity of the isolated product make it promising as a base for developing novel pharmaceuticals. To date, scientific progress has made it possible to expand the scope of applications of UA and comprehend the biological mechanisms mediating its action. This review of the biological activity of UA and its derivatives summarizes publications of the recent decade. New data on the mechanisms of UA action on living organisms are discussed, and ways to modify its biological activity by altering its chemical structure and to control its bioavailability are considered. Special attention is paid to prospects of using semisynthetic UA derivatives as pharmacological agents. Data on the influence of the enantiopurity of UA on its biological activity are analyzed. The first part of the review is dedicated to UA biosynthesis and the biological action of UA and its derivatives on unicellular organisms.     

Recent advances in production of 5-aminolevulinic acid using biological strategies

5-Aminolevulinic acid (5-ALA) is the precursor for the biosynthesis of tetrapyrrole compounds and has broad applications in the medical and agricultural fields. Because of the disadvantages of chemical synthesis methods, microbial production of 5-ALA has drawn intensive attention and has been regarded as an alternative in the last years, especially with the rapid development of metabolic engineering and synthetic biology. In this mini-review, recent advances on the application and microbial production of 5-ALA using novel biological approaches (such as whole-cell enzymatic-transformation, metabolic pathway engineering and cell-free process) are described and discussed in detail. In addition, the challenges and prospects of synthetic biology are discussed.     

Natural production of fluorinated compounds and biotechnological prospects of the fluorinase enzyme

Fluorinated compounds are finding increasing uses in several applications. They are employed in almost all areas of modern society. These compounds are all produced by chemical synthesis and their abundance highly contrasts with fluorinated molecules of natural origin. To date, only some plants and a handful of actinomycetes species are known to produce a small number of fluorinated compounds that include fluoroacetate (FA), some ω-fluorinated fatty acids, nucleocidin, 4-fluorothreonine (4-FT), and the more recently identified (2R3S4S)-5-fluoro-2,3,4-trihydroxypentanoic acid. This largely differs from other naturally produced halogenated compounds, which totals more than 5000. The mechanisms underlying biological fluorination have been uncovered after discovering the first actinomycete species, Streptomyces cattleya, that is capable of producing FA and 4-FT, and a fluorinase has been identified as the enzyme responsible for the formation of the C–F bond. The discovery of this enzyme has opened new perspectives for the biotechnological production of fluorinated compounds and many advancements have been achieved in its application mainly as a biocatalyst for the synthesis of [¹⁸F]-labeled radiotracers for medical imaging. Natural fluorinated compounds may also be derived from abiogenic sources, such as volcanoes and rocks, though their concentrations and production mechanisms are not well known. This review provides an outlook of what is currently known about fluorinated compounds with natural origin. The paucity of these compounds and the biological mechanisms responsible for their production are addressed. Due to its relevance, special emphasis is given to the discovery, characterization and biotechnological potential of the unique fluorinase enzyme.     

Germline Modification and Engineering in Avian Species

Production of genome-edited animals using germline-competent cells and genetic modification tools has provided opportunities for investigation of biological mechanisms in various organisms. The recently reported programmed genome editing technology that can induce gene modification at a target locus in an efficient and precise manner facilitates establishment of animal models. In this regard, the demand for genome-edited avian species, which are some of the most suitable model animals due to their unique embryonic development, has also increased. Furthermore, germline chimera production through long-term culture of chicken primordial germ cells (PGCs) has facilitated research on production of genome-edited chickens. Thus, use of avian germline modification is promising for development of novel avian models for research of disease control and various biological mechanisms. Here, we discuss recent progress in genome modification technology in avian species and its applications and future strategies.     

Arjunolic acid: A new multifunctional therapeutic promise of alternative medicine

Importance of the field

In recent years, a number of studies describing the effective therapeutic strategies of medicinal plants and their active constituents in traditional medicine have been reported. Indeed, tremendous demand for the development and implementation of these plant derived biomolecules in complementary and alternative medicine is increasing and appear to be promising candidates for pharmaceutical industrial research. These new molecules, especially those from natural resources, are considered as potential therapeutic targets, because they are derived from commonly consumed foodstuff and are considered to be safe for humans.

Areas covered in this review

This review highlights the beneficial role of arjunolic acid, a naturally occurring chiral triterpenoid saponin, in various organ pathophysiology and the underlying mechanism of its protective action. Studies on the biochemistry and pharmacology suggest the potential use of arjunolic acid as a novel promising therapeutic strategy.

What the readers will gain

The multifunctional therapeutic application of arjunolic acid has already been documented by its various biological functions including antioxidant, anti-fungal, anti-bacterial, anticholinesterase, antitumor, antiasthmatic, wound healing and insect growth inhibitor activities. The scientific basis behind its therapeutic application as a cardioprotective agent in traditional medicine is justified by its ability to prevent myocardial necrosis and apoptosis, platelet aggregation, coagulation and lowering of blood pressure, heart rate, as well as cholesterol levels. Its antioxidant property coupled with metal chelating property (by its two hydroxyl groups) protects different organs from metal and drug-induced organ pathophysiology. Arjunolic acid also plays a beneficial role in the pathogenesis of diabetes and its associated complications. The mechanism of cytoprotection of arjunolic acid, at least in part, results from the detoxification of reactive oxygen species (ROS) produced in the respective pathophysiology. In addition to its other biological functions, it also possesses vibrant insecticidal properties and it has the potential to be used as a structural molecular framework for the design of molecular receptors in the general area of supramolecular chemistry and nanochemistry. Esters of arjunolic acid function as organogelators which has wide application in designing thermochromic switches and sensor devices. Arjunolic acid derived crown ether is an attractive candidate for the design of molecular receptors, biomimetics and supramolecular systems capable of performing some biological functions.

Home message

This review would provide useful information about the recent progress of natural product research in the domain of clinical science. This review also aims to untie the multifunctional therapeutic application of arjunolic acid, a nanometer-long naturally occurring chiral triterpenoid biomolecule.     

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.     

Recent advances toward the bioconversion of methane and methanol in synthetic methylotrophs

Abundant natural gas reserves, along with increased biogas production, have prompted recent interest in harnessing methane as an industrial feedstock for the production of liquid fuels and chemicals. Methane can either be used directly for fermentation or first oxidized to methanol via biological or chemical means. Methanol is advantageous due to its liquid state under normal conditions. Methylotrophy, defined as the ability of microorganisms to utilize reduced one-carbon compounds like methane and methanol as sole carbon and energy sources for growth, is widespread in bacterial communities. However, native methylotrophs lack the extensive and well-characterized synthetic biology toolbox of platform microorganisms like Escherichia coli, which results in slow and inefficient design-build-test cycles. If a heterologous production pathway can be engineered, the slow growth and uptake rates of native methylotrophs generally limit their industrial potential. Therefore, much focus has been placed on engineering synthetic methylotrophs, or non-methylotrophic platform microorganisms, like E. coli, that have been engineered with synthetic methanol utilization pathways. These platform hosts allow for rapid design-build-test cycles and are well-suited for industrial application at the current time. In this review, recent progress made toward synthetic methylotrophy (including methanotrophy) is discussed. Specifically, the importance of amino acid metabolism and alternative one-carbon assimilation pathways are detailed. A recent study that has achieved methane bioconversion to liquid chemicals in a synthetic E. coli methanotroph is also briefly discussed. We also discuss strategies for the way forward in order to realize the industrial potential of synthetic methanotrophs and methylotrophs.     

Biotechnological production and applications of N-acetyl-d-neuraminic acid: current state and perspectives

N-Acetyl-d-neuraminic acid (Neu5Ac) and its derivates are a very important group of biomolecules because these sugars occupy the terminal positions in numerous macromolecules, such as the glycans of glycoproteins, and are involved in many biological and pathological phenomena. The synthesis and applications of Neu5Ac are attracting much interest due to the potential applications of this compound in the pharmaceutical industry, such as in the synthesis of the anti-flu drug zanamivir. In this review article, we discuss existing knowledge on the biotechnological production and applications of Neu5Ac and also propose some guidelines for future studies.     

Single cell oil production from a newly isolated <Emphasis Type="Italic">Candida viswanathii</Emphasis> Y-E4 and agro-industrial by-products valorization

Microbial lipids have drawn increasing attention in recent years as promising raw materials for biodiesel and added-value compounds production. To this end, new oleaginous yeast, Candida viswanathii Y-E4 was isolated, characterized and used for single cell oil (SCO) production. Physiologic and nutritional parameters optimization was carried out for improved biomass and lipid production. Y-E4 strain was able to use a wide range of substrates, especially C5 and C6 sugars as well as glycerol and hydrophobic substrates. The fatty acid profile analysis showed that oleic acid was the main component produced using different substrates. Batch and fed-bath fermentation were conducted using glucose as carbon source. Lipid production rate is twice higher in fed-batch culture providing a lipid content of 50 % (w/w). To minimize the SCO production cost, C. viswanathii Y-E4 was evaluated for its capacity to use different agro-industrial by-products for microbial oil production and changes in the fatty acid profile were monitored.