scholarly journals Something old, something new: challenges and developments in Aspergillus niger biotechnology

2021 ◽  
Author(s):  
Timothy C. Cairns ◽  
Lars Barthel ◽  
Vera Meyer
Keyword(s):  
Aspergillus Niger ◽  
Secondary Metabolites ◽  
Organic Acids ◽  
Industrial Applications ◽  
Cell Factory ◽  
Special Focus ◽  
Product Portfolio ◽  
Filamentous Ascomycete ◽  
Technological Advances ◽  
Technological Developments

Abstract The filamentous ascomycete fungus Aspergillus niger is a prolific secretor of organic acids, proteins, enzymes and secondary metabolites. Throughout the last century, biotechnologists have developed A. niger into a multipurpose cell factory with a product portfolio worth billions of dollars each year. Recent technological advances, from genome editing to other molecular and omics tools, promise to revolutionize our understanding of A. niger biology, ultimately to increase efficiency of existing industrial applications or even to make entirely new products. However, various challenges to this biotechnological vision, many several decades old, still limit applications of this fungus. These include an inability to tightly control A. niger growth for optimal productivity, and a lack of high-throughput cultivation conditions for mutant screening. In this mini-review, we summarize the current state-of-the-art for A. niger biotechnology with special focus on organic acids (citric acid, malic acid, gluconic acid and itaconic acid), secreted proteins and secondary metabolites, and discuss how new technological developments can be applied to comprehensively address a variety of old and persistent challenges.

scholarly journals Bioproduction of Isoprenoids and Other Secondary Metabolites Using Methanotrophic Bacteria as an Alternative Microbial Cell Factory Option: Current Stage and Future Aspects

Catalysts ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 883 ◽  
Author(s):  
Young Chan Jeon ◽  
Anh Duc Nguyen ◽  
Eun Yeol Lee
Keyword(s):  
Metabolic Engineering ◽  
Secondary Metabolites ◽  
Value Added ◽  
Industrial Applications ◽  
Cell Factory ◽  
Methanotrophic Bacteria ◽  
Microbial Cell Factory ◽  
Future Outlook ◽  
Metabolites Production ◽  
Current Stage

Methane is a promising carbon feedstock for industrial biomanufacturing because of its low price and high abundance. Recent advances in metabolic engineering and systems biology in methanotrophs have made it possible to produce a variety of value-added compounds from methane, including secondary metabolites. Isoprenoids are one of the largest family of secondary metabolites and have many useful industrial applications. In this review, we highlight the current efforts invested to methanotrophs for the production of isoprenoids and other secondary metabolites, including riboflavin and ectoine. The future outlook for improving secondary metabolites production (especially of isoprenoids) using metabolic engineering of methanotrophs is also discussed.

scholarly journals Beyond the biosynthetic gene cluster paradigm: Genome-wide co-expression networks connect clustered and unclustered transcription factors to secondary metabolic pathways

2020 ◽  
Author(s):  
Min Jin Kwon ◽  
Charlotte Steiniger ◽  
Timothy C. Cairns ◽  
Jennifer H. Wisecaver ◽  
Abigail Lind ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Aspergillus Niger ◽  
Secondary Metabolites ◽  
Metabolic Pathways ◽  
Correlation Coefficients ◽  
Genetic Networks ◽  
Cell Factory ◽  
Biosynthetic Gene ◽  
Genome Wide ◽  
Novel Drug

AbstractFungal secondary metabolites are widely used as therapeutics and are vital components of drug discovery programs. A major challenge hindering discovery of novel secondary metabolites is that the underlying pathways involved in their biosynthesis are transcriptionally silent in typical laboratory growth conditions, making it difficult to identify the transcriptional networks that they are embedded in. Furthermore, while the genes participating in secondary metabolic pathways are typically found in contiguous clusters on the genome, known as biosynthetic gene clusters (BGCs), this is not always the case, especially for global and pathway-specific regulators of pathways’ activities. To address these challenges, we used 283 genome-wide gene expression datasets of the ascomycete cell factory Aspergillus niger generated during growth under 155 different conditions to construct two gene co-expression networks based on Spearman’s correlation coefficients (SCC) and on mutual rank-transformed Pearson’s correlation coefficients (MR-PCC). By mining these networks, we predicted six transcription factors named MjkA – MjkF to concomitantly regulate secondary metabolism in A. niger. Over-expression of each transcription factor using the Tet-on cassette modulated production of multiple secondary metabolites. We found that the SCC and MR-PCC approaches complemented each other, enabling the delineation of global (SCC) and pathway-specific (MR-PCC) transcription factors, respectively. These results highlight the great potential of co-expression network approaches to identify and activate fungal secondary metabolic pathways and their products. More broadly, we argue that novel drug discovery programs in fungi should move beyond the BGC paradigm and focus on understanding the global regulatory networks in which secondary metabolic pathways are embedded.ImportanceThere is an urgent need for novel bioactive molecules in both agriculture and medicine. The genomes of fungi are thought to contain vast numbers of metabolic pathways involved in the biosynthesis of secondary metabolites with diverse bioactivities. Because these metabolites are biosynthesized only under specific conditions, the vast majority of fungal pharmacopeia awaits discovery. To discover the genetic networks that regulate the activity of secondary metabolites, we examined the genome-wide profiles of gene activity of the cell factory Aspergillus niger across hundreds of conditions. By constructing global networks that link genes with similar activities across conditions, we identified six global and pathway-specific regulators of secondary metabolite biosynthesis. Our study shows that elucidating the behavior of the genetic networks of fungi under diverse conditions harbors enormous promise for understanding fungal secondary metabolism, which ultimately may lead to novel drug candidates.

Bioactive Secondary Metabolites from Endophytic Fungi

2020 ◽  
Vol 27 (11) ◽  
pp. 1836-1854 ◽  
Author(s):  
Elena Ancheeva ◽  
Georgios Daletos ◽  
Peter Proksch
Keyword(s):  
Secondary Metabolites ◽  
Endophytic Fungi ◽  
Host Plants ◽  
Biological Activities ◽  
Cytotoxic Agents ◽  
Special Focus ◽  
Plant Metabolites ◽  
Direct Production ◽  
Bioactive Secondary Metabolites ◽  
Fungal Genes

Background: Endophytes represent a complex community of microorganisms colonizing asymptomatically internal tissues of higher plants. Several reports have shown that endophytes enhance the fitness of their host plants by direct production of bioactive secondary metabolites, which are involved in protecting the host against herbivores and pathogenic microbes. In addition, it is increasingly apparent that endophytes are able to biosynthesize medicinally important “phytochemicals”, originally believed to be produced only by their host plants. Objective: The present review provides an overview of secondary metabolites from endophytic fungi with pronounced biological activities covering the literature between 2010 and 2017. Special focus is given on studies aiming at exploration of the mode of action of these metabolites towards the discovery of leads from endophytic fungi. Moreover, this review critically evaluates the potential of endophytic fungi as alternative sources of bioactive “plant metabolites”. Results: Over the past few years, several promising lead structures from endophytic fungi have been described in the literature. In this review, 65 metabolites are outlined with pronounced biological activities, primarily as antimicrobial and cytotoxic agents. Some of these metabolites have shown to be highly selective or to possess novel mechanisms of action, which hold great promises as potential drug candidates. Conclusion: Endophytes represent an inexhaustible reservoir of pharmacologically important compounds. Moreover, endophytic fungi could be exploited for the sustainable production of bioactive “plant metabolites” in the future. Towards this aim, further insights into the dynamic endophyte - host plant interactions and origin of endophytic fungal genes would be of utmost importance.

scholarly journals Profiles of Secondary Metabolites (Phenolic Acids, Carotenoids, Anthocyanins, and Galantamine) and Primary Metabolites (Carbohydrates, Amino Acids, and Organic Acids) during Flower Development in Lycoris radiata

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 248
Author(s):  
Chang Ha Park ◽  
Hyeon Ji Yeo ◽  
Ye Jin Kim ◽  
Bao Van Nguyen ◽  
Ye Eun Park ◽  
...  
Keyword(s):  
Amino Acids ◽  
Secondary Metabolites ◽  
Organic Acids ◽  
Phenolic Acids ◽  
Flower Development ◽  
Developmental Stages ◽  
Tca Cycle ◽  
Primary And Secondary Metabolites ◽  
Hydrophilic Compounds ◽  
Tca Cycle Intermediates

This study aimed to elucidate the variations in primary and secondary metabolites during Lycorisradiata flower development using high performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC-TOFMS). The result showed that seven carotenoids, seven phenolic acids, three anthocyanins, and galantamine were identified in the L. radiata flowers. Most secondary metabolite levels gradually decreased according to the flower developmental stages. A total of 51 metabolites, including amines, sugars, sugar intermediates, sugar alcohols, amino acids, organic acids, phenolic acids, and tricarboxylic acid (TCA) cycle intermediates, were identified and quantified using GC-TOFMS. Among the hydrophilic compounds, most amino acids increased during flower development; in contrast, TCA cycle intermediates and sugars decreased. In particular, glutamine, asparagine, glutamic acid, and aspartic acid, which represent the main inter- and intracellular nitrogen carriers, were positively correlated with the other amino acids and were negatively correlated with the TCA cycle intermediates. Furthermore, quantitation data of the 51 hydrophilic compounds were subjected to partial least-squares discriminant analyses (PLS-DA) to assess significant differences in the metabolites of L. radiata flowers from stages 1 to 4. Therefore, this study will serve as the foundation for a biochemical approach to understand both primary and secondary metabolism in L. radiata flower development.

scholarly journals Clinical and immunological effects of mRNA vaccines in malignant diseases

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Annkristin Heine ◽  
Stefan Juranek ◽  
Peter Brossart
Keyword(s):  
Immune Responses ◽  
Messenger Rna ◽  
Immune Escape ◽  
Special Focus ◽  
Potential Efficacy ◽  
Protective Antibodies ◽  
Technological Developments ◽  
Broad Variety ◽  
Antigen Loss

AbstractIn vitro-transcribed messenger RNA-based therapeutics represent a relatively novel and highly efficient class of drugs. Several recently published studies emphasize the potential efficacy of mRNA vaccines in treating different types of malignant and infectious diseases where conventional vaccine strategies and platforms fail to elicit protective immune responses. mRNA vaccines have lately raised high interest as potent vaccines against SARS-CoV2. Direct application of mRNA or its electroporation into dendritic cells was shown to induce polyclonal CD4+ and CD8+ mediated antigen-specific T cell responses as well as the production of protective antibodies with the ability to eliminate transformed or infected cells. More importantly, the vaccine composition may include two or more mRNAs coding for different proteins or long peptides. This enables the induction of polyclonal immune responses against a broad variety of epitopes within the encoded antigens that are presented on various MHC complexes, thus avoiding the restriction to a certain HLA molecule or possible immune escape due to antigen-loss. The development and design of mRNA therapies was recently boosted by several critical innovations including the development of technologies for the production and delivery of high quality and stable mRNA. Several technical obstacles such as stability, delivery and immunogenicity were addressed in the past and gradually solved in the recent years.This review will summarize the most recent technological developments and application of mRNA vaccines in clinical trials and discusses the results, challenges and future directions with a special focus on the induced innate and adaptive immune responses.

A study of P release from Fe-P and Ca-P via the organic acids secreted by Aspergillus niger

2021 ◽  
Author(s):  
Da Tian ◽  
Liyan Wang ◽  
Jun Hu ◽  
Liangliang Zhang ◽  
Ningning Zhou ◽  
...  
Keyword(s):  
Aspergillus Niger ◽  
Organic Acids ◽  
P Release

scholarly journals Functionalized Carbon Nanotubes (CNTs) for Water and Wastewater Treatment: Preparation to Application

2021 ◽  
Vol 13 (10) ◽  
pp. 5717
Author(s):  
Mian Muhammad-Ahson Aslam ◽  
Hsion-Wen Kuo ◽  
Walter Den ◽  
Muhammad Usman ◽  
Muhammad Sultan ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Wastewater Treatment ◽  
Water Resources ◽  
Large Scale ◽  
Industrial Applications ◽  
Biological Species ◽  
Special Focus ◽  
Water And Wastewater Treatment ◽  
Adsorption Sites ◽  
Water And Wastewater

As the world human population and industrialization keep growing, the water availability issue has forced scientists, engineers, and legislators of water supply industries to better manage water resources. Pollutant removals from wastewaters are crucial to ensure qualities of available water resources (including natural water bodies or reclaimed waters). Diverse techniques have been developed to deal with water quality concerns. Carbon based nanomaterials, especially carbon nanotubes (CNTs) with their high specific surface area and associated adsorption sites, have drawn a special focus in environmental applications, especially water and wastewater treatment. This critical review summarizes recent developments and adsorption behaviors of CNTs used to remove organics or heavy metal ions from contaminated waters via adsorption and inactivation of biological species associated with CNTs. Foci include CNTs synthesis, purification, and surface modifications or functionalization, followed by their characterization methods and the effect of water chemistry on adsorption capacities and removal mechanisms. Functionalized CNTs have been proven to be promising nanomaterials for the decontamination of waters due to their high adsorption capacity. However, most of the functional CNT applications are limited to lab-scale experiments only. Feasibility of their large-scale/industrial applications with cost-effective ways of synthesis and assessments of their toxicity with better simulating adsorption mechanisms still need to be studied.

scholarly journals Two-Side Laser Processing Method for Producing High Aspect Ratio Microholes

2017 ◽  
Vol 5 (4) ◽  
Author(s):  
Vahid Nasrollahi ◽  
Pavel Penchev ◽  
Stefan Dimov ◽  
Lars Korner ◽  
Richard Leach ◽  
...  
Keyword(s):  
Cross Sections ◽  
Laser Processing ◽  
Industrial Applications ◽  
Laser Drilling ◽  
Special Focus ◽  
Geometrical Accuracy ◽  
Aspect Ratios ◽  
Wide Range ◽  
High Flexibility ◽  
Accuracy And Repeatability

Laser microprocessing is a very attractive option for a growing number of industrial applications due to its intrinsic characteristics, such as high flexibility and process control and also capabilities for noncontact processing of a wide range of materials. However, there are some constrains that limit the applications of this technology, i.e., taper angles on sidewalls, edge quality, geometrical accuracy, and achievable aspect ratios of produced structures. To address these process limitations, a new method for two-side laser processing is proposed in this research. The method is described with a special focus on key enabling technologies for achieving high accuracy and repeatability in two-side laser drilling. The pilot implementation of the proposed processing configuration and technologies is discussed together with an in situ, on-machine inspection procedure to verify the achievable positional and geometrical accuracy. It is demonstrated that alignment accuracy better than 10 μm is achievable using this pilot two-side laser processing platform. In addition, the morphology of holes with circular and square cross sections produced with one-side laser drilling and the proposed method was compared in regard to achievable aspect ratios and holes' dimensional and geometrical accuracy and thus to make conclusions about its capabilities.

scholarly journals IMPLEMENTASI MODEL PEMURIDAN KONTEKSTUAL SEBAGAI PANGGILAN PELAYANAN TERHADAP GENERASI MILENIAL DI ERA INDUSTRI 4.0

2020 ◽  
Author(s):  
Febriani
Keyword(s):  
Industrial Revolution ◽  
Qualitative Approach ◽  
Christian Identity ◽  
Technological Advances ◽  
The World ◽  
Technological Developments ◽  
Discipleship Model ◽  
Service Call

ABSTRAK - Arus globalisasi yang mendunia sudah tidak dapat dibendung lagi keberadaannya di negara Indonesia. Indonesia menjadi salah satu dari berbagai negara yang telah dipengaruhi oleh perkembangan teknologi dan iptek yang semakin canggih, sehingga dunia kini telah memasuki era industri 4.0. Generasi milenial adalah salah satu kelompok yang dipengaruhi oleh perkembangan teknologi yang serba instan, bahkan peran penting generasi milenial sudah mulai surut tergantikan oleh kemajuan teknologi. Menghadapi tantangan tersebut diperlukan solusi yang solutif yaitu mengimplementasikan model pemuridan kontekstual sebagai panggilan pelayanan terhadap generasi milenial di era industri 4.0, sehingga membentuk generasi milenial supaya beridentitas Kristen dan bertumbuh menjadi dewasa dalam iman. Pendekatan yang dilakukan adalah dengan pendekatan kualitatif yang melibatkan studi pustaka. Penelitian ini menghasilkan kesimpulan bahwa model pemuridan kontekstual layak dijadikan pedoman dalam mengarahkan para generasi milenial di era indutri 4.0 agar mampu bertahan (survive) dalam perkembangan zaman yang semakin canggih.Kata kunci : Pemuridan, Kontekstual, Panggilan Pelayanan, Generasi Milenial, Revolusi Industri 4.0ABSTRACT - The current global globalization can not be dammed anymore its existence in the country of Indonesia. Indonesia has become one of a variety of countries that have been influenced by increasingly sophisticated technological and technological developments, so that the world has now entered the industrial era 4.0. Millennials have become one of those groups influenced by the development of instantaneous technology, even the important role of millennials has begun to subside replaced by technological advances. Facing these challenges requires a solution that is to implement a model of contextual discipleship as a service call to millennials in the industrial era 4.0, thus forming millennial generations so that Christian identity and growing into adulthood in the faith. The approach taken is a qualitative approach that involves the study of literature. This research concludes that the contextual discipleship model deserves to be used as a guideline in directing millennial generations in the 4.0 industry era to be able to survive in the development of increasingly sophisticated times.Key Words : Discipleship, Contextual, Service Call, Milennial Generation, Industrial Revolution 4.0

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