scholarly journals Synthesis of oxyfunctionalized NSAID metabolites by microbial biocatalysts

2018 ◽  
Author(s):  
Jan M. Klenk ◽  
Lisa Kontny ◽  
Bernd A. Nebel ◽  
Bernhard Hauer
Keyword(s):  
Filamentous Fungi ◽  
Proteome Analysis ◽  
Environmental Studies ◽  
New Drugs ◽  
Synthetic Methods ◽  
Toxic Substances ◽  
Drug Metabolites ◽  
Cell Factories ◽  
Major Interest ◽  
Microbial Biocatalysts

AbstractThe synthesis of valuable metabolites and degradation intermediates of drugs, like non-steroidal anti-inflammatory drugs (NSAIDs), are substantially for toxicological and environmental studies, but efficient synthesis strategies and the metabolite availability are still challenging aspects. To overcome these bottlenecks filamentous fungi as microbial biocatalysts were applied. Different NSAIDs like diclofenac, ibuprofen, naproxen and mefenamic acid could be oxyfunctionalized to produce human metabolites in isolated yields of up to 99% using 1 g L−1 of substrate. Thereby the biotransformations using Beauveria bassiana, Clitocybe nebularis or Mucor hiemalis surpass previous reported chemical, microbial and P450-based routes in terms of efficiency. In addition to different hydroxylated compounds of diclofenac, a novel metabolite, 3’,4’-dihydroxydiclofenac, has been catalyzed by B. bassiana and the responsible P450s were identified by proteome analysis. The applied filamentous fungi present an interesting alternative, microbial biocatalysts platform for the production of valuable oxyfunctionalized drug metabolites.ImportanceThe occurrence of pharmaceutically active compounds, such as diclofenac and its metabolites, in the environment, in particular in aquatic systems, is of increasing concern because of the increased application of drugs. Standards of putative metabolites are therefore necessary for environmental studies. Moreover, pharmaceutical research and development requires assessment of the bioavailability, toxicity and metabolic fate of potential new drugs to ensure its safety for users and the environment. Since most of the reactions in the early pharmacokinetics of drugs are oxyfunctionalizations catalysed by P450s, oxyfunctionalized metabolites are of major interest. However, to assess these metabolites chemical synthesis often suffer from multistep reactions, toxic substances, polluting conditions and achieve only low regioselectivity. Biocatalysis can contribute to this by using microbial cell factories. The significance of our research is to complement or even exceed synthetic methods for the production of oxyfunctionalized drug metabolites.

Membrane traffic related to endosome dynamics and protein secretion in filamentous fungi

2021 ◽  
Author(s):  
Yujiro Higuchi
Keyword(s):  
Filamentous Fungi ◽  
Protein Secretion ◽  
Secretory Pathway ◽  
Molecular Mechanisms ◽  
Membrane Traffic ◽  
Early Endosome ◽  
Protein Glycosylation ◽  
Hyphal Cell ◽  
Cell Factories ◽  
Membrane Contacts

ABSTRACT In eukaryotic cells, membrane-surrounded organelles are orchestrally organized spatiotemporally under environmental situations. Among such organelles, vesicular transports and membrane contacts occur to communicate each other, so-called membrane traffic. Filamentous fungal cells are highly polarized and thus membrane traffic is developed to have versatile functions. Early endosome (EE) is an endocytic organelle that dynamically exhibits constant long-range motility through the hyphal cell, which is proven to have physiological roles, such as other organelle distribution and signal transduction. Since filamentous fungal cells are also considered as cell factories, to produce valuable proteins extracellularly, molecular mechanisms of secretory pathway including protein glycosylation have been well investigated. In this review, molecular and physiological aspects of membrane traffic especially related to EE dynamics and protein secretion in filamentous fungi are summarized, and perspectives for application are also described.

scholarly journals A Critical Review on the Ubiquitous Role of Filamentous Fungi in Pollution Mitigation

2020 ◽  
Vol 6 (4) ◽  
pp. 295-309 ◽  
Author(s):  
Jorge A. Ferreira ◽  
Sunita Varjani ◽  
Mohammad J. Taherzadeh
Keyword(s):  
Filamentous Fungi ◽  
Knowledge Integration ◽  
Anthropogenic Activities ◽  
Inorganic Compounds ◽  
Fungal Growth ◽  
Analytical Techniques ◽  
Environmental Studies ◽  
Anthropogenic Pollution ◽  
Holistic Approach ◽  
Pollution Mitigation

Abstract Propose of Review Anthropogenic activities are saturating wastewater treatment plants and the environment with an increasing range of organic and inorganic compounds, impairing ecosystems and health. Filamentous fungi, with characteristic filamentous growth, array of extracellular and intracellular enzymes, production of surfactants, cell wall biosorption properties, and symbiotic momentum, can contribute to a paradigm shift on the perception of anthropogenic pollution. This review provides a critical analysis of the main bottlenecks for feasible filamentous fungus-including processes and proposes a holistic approach for pollution mitigation using filamentous fungi. Recent Findings Filamentous fungi can convert ordinary sidestreams into, e.g., feed proteins and biofuels. Economic and environmental studies support integration in established processes. Intersectoral initiatives, and economic and environmental studies, need to be motivated to increase the range of processes. Although massively studied, the transfer of fungal processes for the removal of micropollutants into real matrices is difficult. It needs to be supported by omics technologies for the study of microbial networks, and by efficient analytical techniques to clarify detoxification potential. The area can benefit from knowledge integration from fungal growth in ordinary sidestreams, and from economic and environmental studies. Summary The interest in filamentous fungi for pollution mitigation is corroborated by an overwhelming amount of research; however, no full-scale applications are currently known. Environmental pollution is a reality and production of ordinary sidestreams and micropollutant-rich wastewaters continuous. The establishment of filamentous fungal processes needs collaboration among governmental authorities, industries, and academics in order to tackle knowledge gaps within the area and propose a holistic approach.

scholarly journals Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi

mSystems ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Jens Christian Nielsen ◽  
Sylvain Prigent ◽  
Sietske Grijseels ◽  
Mhairi Workman ◽  
Boyang Ji ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Secondary Metabolite ◽  
Filamentous Fungi ◽  
Metabolic Regulation ◽  
Fungal Species ◽  
Efficient Production ◽  
Fungal Cell ◽  
Fungal Metabolism ◽  
Cell Factories

ABSTRACTFilamentous fungi possess great potential as sources of medicinal bioactive compounds, such as antibiotics, but efficient production is hampered by a limited understanding of how their metabolism is regulated. We investigated the metabolism of six secondary metabolite-producing fungi of thePenicilliumgenus during nutrient depletion in the stationary phase of batch fermentations and assessed conserved metabolic responses across species using genome-wide transcriptional profiling. A coexpression analysis revealed that expression of biosynthetic genes correlates with expression of genes associated with pathways responsible for the generation of precursor metabolites for secondary metabolism. Our results highlight the main metabolic routes for the supply of precursors for secondary metabolism and suggest that the regulation of fungal metabolism is tailored to meet the demands for secondary metabolite production. These findings can aid in identifying fungal species that are optimized for the production of specific secondary metabolites and in designing metabolic engineering strategies to develop high-yielding fungal cell factories for production of secondary metabolites.IMPORTANCESecondary metabolites are a major source of pharmaceuticals, especially antibiotics. However, the development of efficient processes of production of secondary metabolites has proved troublesome due to a limited understanding of the metabolic regulations governing secondary metabolism. By analyzing the conservation in gene expression across secondary metabolite-producing fungal species, we identified a metabolic signature that links primary and secondary metabolism and that demonstrates that fungal metabolism is tailored for the efficient production of secondary metabolites. The insight that we provide can be used to develop high-yielding fungal cell factories that are optimized for the production of specific secondary metabolites of pharmaceutical interest.

scholarly journals Genome-Wide Chromatin Immunoprecipitation Sequencing Analysis of the Penicillium chrysogenum Velvet Protein PcVelA Identifies Methyltransferase PcLlmA as a Novel Downstream Regulator of Fungal Development

mSphere ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Kordula Becker ◽  
Sandra Ziemons ◽  
Katharina Lentz ◽  
Michael Freitag ◽  
Ulrich Kück
Keyword(s):  
Next Generation Sequencing ◽  
Secondary Metabolism ◽  
Filamentous Fungi ◽  
Chromatin Immunoprecipitation ◽  
Next Generation ◽  
Content Type ◽  
Major Interest ◽  
Lactam Antibiotic ◽  
Velvet Complex ◽  
Generation Sequencing

ABSTRACT Filamentous fungi are of major interest for biotechnological and pharmaceutical applications. This is due mainly to their ability to produce a wide variety of secondary metabolites, many of which are relevant as antibiotics. One of the most prominent examples is penicillin, a β-lactam antibiotic that is produced on the industrial scale by fermentation of P. chrysogenum. In recent years, the multisubunit protein complex velvet has been identified as one of the key regulators of fungal secondary metabolism and development. However, until recently, only a little has been known about how velvet mediates regulation at the molecular level. To address this issue, we performed ChIP-seq (chromatin immunoprecipitation in combination with next-generation sequencing) on and follow-up analysis of PcVelA, the core component of the velvet complex in P. chrysogenum. We demonstrate direct involvement of velvet in transcriptional control and present the putative methyltransferase PcLlmA as a new downstream factor and interaction partner of PcVelA. Penicillium chrysogenum is the sole industrial producer of the β-lactam antibiotic penicillin, which is the most commonly used drug for treating bacterial infections. In P. chrysogenum and other filamentous fungi, secondary metabolism and morphogenesis are controlled by the highly conserved multisubunit velvet complex. Here we present the first chromatin immunoprecipitation next-generation sequencing (ChIP-seq) analysis of a fungal velvet protein, providing experimental evidence that a velvet homologue in P. chrysogenum (PcVelA) acts as a direct transcriptional regulator at the DNA level in addition to functioning as a regulator at the protein level in P. chrysogenum, which was previously described. We identified many target genes that are related to processes known to be dependent on PcVelA, e.g., secondary metabolism as well as asexual and sexual development. We also identified seven PcVelA target genes that encode putative methyltransferases. Yeast two-hybrid and bimolecular fluorescence complementation analyses showed that one of the putative methyltransferases, PcLlmA, directly interacts with PcVelA. Furthermore, functional characterization of PcLlmA demonstrated that this protein is involved in the regulation of conidiosporogenesis, pellet formation, and hyphal morphology, all traits with major biotechnological relevance. IMPORTANCE Filamentous fungi are of major interest for biotechnological and pharmaceutical applications. This is due mainly to their ability to produce a wide variety of secondary metabolites, many of which are relevant as antibiotics. One of the most prominent examples is penicillin, a β-lactam antibiotic that is produced on the industrial scale by fermentation of P. chrysogenum. In recent years, the multisubunit protein complex velvet has been identified as one of the key regulators of fungal secondary metabolism and development. However, until recently, only a little has been known about how velvet mediates regulation at the molecular level. To address this issue, we performed ChIP-seq (chromatin immunoprecipitation in combination with next-generation sequencing) on and follow-up analysis of PcVelA, the core component of the velvet complex in P. chrysogenum. We demonstrate direct involvement of velvet in transcriptional control and present the putative methyltransferase PcLlmA as a new downstream factor and interaction partner of PcVelA.

scholarly journals Isolation of Filamentous Fungi Species Contaminating Some Nigerian Food Commodities

2014 ◽  
Vol 4 (1) ◽  
pp. 38 ◽  
Author(s):  
Mary Augustina Egbuta ◽  
Mulunda Mwanza ◽  
Patrick Berka Njobeh ◽  
Judith Zanele Phoku ◽  
Cynthia Adaku Chilaka ◽  
...  
Keyword(s):  
Filamentous Fungi ◽  
Fungal Species ◽  
Nucleotide Sequencing ◽  
Malt Extract ◽  
Toxic Substances ◽  
Molecular Method ◽  
Microscopic Evaluation ◽  
Identification Of Fungi ◽  
Polymerase Chain ◽  
Food Commodities

<p>Samples of maize, rice, cocoa and cocoa-based powder beverage) collected from different stores and markets in south-western Nigeria were screened for filamentous fungi contamination using conventional and molecular methods. Samples were cultured aseptically on potato dextrose agar (PDA), ohio agricultural experimental agar (OEASA), Malt Extract Agar (MEA) and Czapek Yeast Agar (CYA) prior to fungi isolation. Conventional methods comprising of macroscopic and microscopic evaluation of isolated fungi species were implemented in the analysis for identification of fungi species. Molecular method of identification involved DNA extraction, Polymerase chain Reaction (PCR) using ITS-1/ITS-4 primer pair and nucleotide sequencing. Results obtained indicated a range of filamentous fungi genus including <em>Aspergillus</em>, <em>Penicillium</em>, <em>Fusarium</em>, <em>Alternaria,</em> <em>Cladosporium</em> and <em>Rhizopus</em> contaminating the food commodities with <em>Aspergillus</em> and <em>Penicillium</em> species dominating most of the samples. High incidences were recorded for <em>Aspergillus flavus</em>, <em>Aspergillus niger</em> and <em>Aspergillus fumigatus</em> in most of the samples screened. The occurrence of these filamentous fungal species pose a reason for concern as most of these fungal species are known producers of toxic substances. This study was carried out to contribute to mycological screening of different Nigerian food commodities for a variety of filamentous fungi species.</p>

New Frontiers in the Prevention, Diagnosis, and Treatment of Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Leonardo Guzman-Martinez ◽  
Camila Calfío ◽  
Gonzalo A. Farias ◽  
Cristian Vilches ◽  
Raul Prieto ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Life ◽  
Healthy Aging ◽  
Integrated Approach ◽  
New Drugs ◽  
Toxic Substances ◽  
Brain Disorder ◽  
Screening Programs ◽  
Nutraceutical Compounds

One of the major puzzles in medical research and public health systems worldwide is Alzheimer’s disease (AD), reaching nowadays a prevalence near 50 million people. This is a multifactorial brain disorder characterized by progressive cognitive impairment, apathy, and mood and neuropsychiatric disorders. The main risk of AD is aging; a normal biological process associated with a continuum dynamic involving a gradual loss of people’s physical capacities, but with a sound experienced view of life. Studies suggest that AD is a break from normal aging with changes in the powerful functional capacities of neurons as well as in the mechanisms of neuronal protection. In this context, an important path has been opened toward AD prevention considering that there are elements of nutrition, daily exercise, avoidance of toxic substances and drugs, an active social life, meditation, and control of stress, to achieve healthy aging. Here, we analyze the involvement of such factors and how to control environmental risk factors for a better quality of life. Prevention as well as innovative screening programs for early detection of the disease using reliable biomarkers are becoming critical to control the disease. In addition, the failure of traditional pharmacological treatments and search for new drugs has stimulated the emergence of nutraceutical compounds in the context of a “multitarget” therapy, as well as mindfulness approaches shown to be effective in the aging, and applied to the control of AD. An integrated approach involving all these preventive factors combined with novel pharmacological approaches should pave the way for the future control of the disease.

scholarly journals GREEN SYNTHESIS, GREEN CHEMISTRY, AND ENVIRONMENTAL SUSTAINABILITY

2021 ◽  
Vol 7 (1) ◽  
pp. 18-27
Author(s):  
Mohammad Asif
Keyword(s):  
Green Chemistry ◽  
Green Synthesis ◽  
Environmental Sustainability ◽  
Industrial Applications ◽  
Vital Role ◽  
New Drugs ◽  
Synthetic Methods ◽  
Synthesis Methods ◽  
Waste Products ◽  
By Products

Purpose: The chemistry society has activated to expand new chemistry that is less destructive to the environment and human health. This approach has extensive interest and designated as green chemistry, environmentally friendly chemistry, clean chemistry, and atom economy. Methodology: There is advancement toward involved chemistry with the facts and do not prevent the properties of the target compound or the efficacy of particular solvents or reagents. The use of chemistry in a way that maximizes benefits while reducing adverse effects has come to be green chemistry. Main findings: Reduce the use and formation of harmful products or by-products. Presently maximum pollution to the environment is caused by some chemical industries. So, need to design and develop synthetic methods in such a way that the waste products are lowest and have no effect on the environment and their handy disposal. Applications of the work: Green chemistry plays a vital role in pharmaceuticals for developing new drugs which are less toxic, more effective with low side effects. The novelty of the work: The industries performing manufacturing using green synthesis methods to carrying out their productions have positive impacts on environmental sustainability. This review is looking ahead at longer-term challenges and prospects in research, industrial applications, and education.

scholarly journals A Dynamic Approach to a Comparative Evaluation of Financial Performance of Sections and Sectors of the Polish Economy

2019 ◽  
Vol 4 (343) ◽  
pp. 39-52
Author(s):  
Wanda Skoczylas ◽  
Barbara Batóg
Keyword(s):  
Financial Performance ◽  
Comparative Evaluation ◽  
Financial Analysis ◽  
Synthetic Methods ◽  
Dynamic Approach ◽  
Financial Independence ◽  
Major Interest ◽  
Dynamic Version ◽  
Polish Economy

Financial performance of companies and their groups is of major interest to all stakeholders. As a result, they assess categories such as profitability, financial liquidity, financial independence, and risk. Separate analyses carried out for each of those elements alone do not always deliver conclusive findings, which is where synthetic methods are helpful. A ranking based on the taxonomic measure of development is one of such methods. The aim of the paper is, firstly, to present opportunities for using a dynamic version of the taxonomic measure of development in a comparative and complex assessment of financial performance in PKD divisions (Polish Classification of Activity), and, secondly, to evaluate changes in this area in the years 2014–2016. The data used for developing the ranking were sourced from the joint publication of industry indicators by the Financial Analysis Commission at the Research Council of the Accountants Association in Poland and InfoCredit, and from the Statistics Poland.

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