Systematic analysis of the lysine malonylome in Sanghuangporus sanghuang

Abstract Background Sanghuangporus sanghuang is a well-known traditional medicinal mushroom associated with mulberry. Despite the properties of this mushroom being known for many years, the regulatory mechanisms of bioactive compound biosynthesis in this medicinal mushroom are still unclear. Lysine malonylation is a posttranslational modification that has many critical functions in various aspects of cell metabolism. However, at present we do not know its role in S. sanghuang. In this study, a global investigation of the lysine malonylome in S. sanghuang was therefore carried out. Results In total, 714 malonyl modification sites were matched to 255 different proteins. The analysis indicated that malonyl modifications were involved in a wide range of cellular functions and displayed a distinct subcellular localization. Bioinformatics analysis indicated that malonylated proteins were engaged in different metabolic pathways, including glyoxylate and dicarboxylate metabolism, glycolysis/gluconeogenesis, and the tricarboxylic acid (TCA) cycle. Notably, a total of 26 enzymes related to triterpene and polysaccharide biosynthesis were found to be malonylated, indicating an indispensable role of lysine malonylation in bioactive compound biosynthesis in S. sanghuang. Conclusions These findings suggest that malonylation is associated with many metabolic pathways, particularly the metabolism of the bioactive compounds triterpene and polysaccharide. This paper represents the first comprehensive survey of malonylation in S. sanghuang and provides important data for further study on the physiological function of lysine malonylation in S. sanghuang and other medicinal mushrooms.

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Systematic Analysis of the Lysine Malonylome in Sanghuangporus Sanghuang

10.21203/rs.3.rs-128142/v1 ◽

2020 ◽

Author(s):

Tong Wang ◽

Guangyuan Wang ◽

Guoli Zhang ◽

Ranran Hou ◽

Liwei Zhou ◽

...

Keyword(s):

Liquid Chromatography ◽

Metabolic Pathways ◽

High Performance ◽

Tca Cycle ◽

Systematic Analysis ◽

Polysaccharide Biosynthesis ◽

Wide Range ◽

Proteomics Technology ◽

Liquid Chromatography Tandem Mass ◽

Comprehensive Survey

Abstract Background: Sanghuangporus sanghuang is a well-known traditional medicinal mushroom associated with mulberry, which has enormous economic and medical value. Despite being known for many years, proteomics studies of S. sanghuang have not been reported. In this paper, a series of technologies, such as high-performance liquid chromatography (HPLC) classification technology, malonyl peptide segment enrichment technology and proteomics technology, are combined to study the qualitative analysis of malonylation in S. sanghuang.Results: Strategies for qualitative proteomics included malonyl enrichment and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). In total, 714 malonyl modification sites were matched to 255 different proteins. The analysis indicated that malonyl modifications are involved in a wide range of acellular functions and displayed a distinct subcellular localization.Bioinformatics analysis indicates that malonylated proteins are engaged in different metabolic pathways, including glyoxylate and dicarboxylate metabolism, glycolysis/gluconeogenesis, and the tricarboxylic acid (TCA) cycle; consequently, a total of 26 enzymes related to triterpene and polysaccharide biosynthesis were found to be malonylated.Conclusions: These findings suggest that malonylation is associated with many metabolic pathways, particularly the metabolism of bioactive compounds. This paper provides the first comprehensive survey of malonylation in S. sanghuang.

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Ref-1 Redox Activity Alters Cancer Cell Metabolism in Pancreatic Cancer: Exploiting This Novel Finding as a Potential Target

10.21203/rs.3.rs-125304/v1 ◽

2020 ◽

Author(s):

Silpa Gampala ◽

Fenil Shah ◽

Xiaoyu Lu ◽

Hye-ran Moon ◽

George Sandusky ◽

...

Keyword(s):

Pancreatic Cancer ◽

Mitochondrial Function ◽

Metabolic Pathways ◽

Cell Metabolism ◽

Tca Cycle ◽

Redox Signaling ◽

Qrt Pcr ◽

Cancer Cell Metabolism

Abstract Background: Pancreatic cancer is a complex disease with a desmoplastic stroma, extreme hypoxia, and inherent resistance to therapy. Understanding the signaling and adaptive response of such an aggressive cancer is key to making advances in therapeutic efficacy. Redox factor-1 (Ref-1), a redox signaling protein, regulates the DNA binding activity of several transcription factors (TFs), including HIF-1α, STAT3 and NFκB . The conversion of these TFs from an oxidized to reduced state lead to enhancement of their DNA binding. In our previously published work, knockdown of Ref-1 under normoxia resulted in altered gene expression patterns on pathways including EIF2, protein kinase A, and mTOR. In this study, single cell RNA sequencing (scRNA-seq) and proteomics were used to explore the effects of Ref-1 on metabolic pathways under hypoxia.Methods: scRNA-seq comparing pancreatic cancer cells expressing less than 20% of the Ref-1 protein was analyzed using left truncated mixture Gaussian model and validated using proteomics and qRT-PCR. The impact of knocking down Ref-1 under hypoxia was dramatic on the mitochondria and metabolic pathways. Ref-1’s role in mitochondrial function was confirmed using mitochondrial function assays and qRT-PCR. Further, the effect of Ref-1 redox function inhibition against pancreatic cancer metabolism was assayed using 3D co-culture in vitro and xenograft studies in vivo and compared to Devimistat, a drug that disrupts mitochondrial metabolism.Results: Distinct transcriptional variation in central metabolism, cell cycle, apoptosis, immune response, and genes downstream of a series of signaling pathways and transcriptional regulatory factors were identified in Ref-1 knockdown vs Scrambled control from the scRNA-seq data. Mitochondrial DEG subsets downregulated with Ref-1 knockdown were significantly reduced following Ref-1 redox inhibition and more dramatically in combination with Devimistat in vitro. Mitochondrial function assays demonstrated that Ref-1 knockdown and Ref-1 redox signaling inhibition decreased utilization of TCA cycle substrates and slowed the growth of pancreatic cancer co-culture spheroids. In vivo xenograft studies demonstrated that tumor reduction was potent with Ref-1 redox inhibitor similar to Devimistat.Conclusion: Ref-1 redox signaling inhibition conclusively alters cancer cell metabolism by causing TCA cycle dysfunction while also reducing the pancreatic tumor growth in vitro as well as in vivo.

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Optimization of biomass production with enhanced bioactive compound content by the medicinal mushroom Ganoderma australe under submerged culture

Planta Medica ◽

10.1055/s-0031-1282279 ◽

2011 ◽

Vol 77 (12) ◽

Author(s):

LM Papaspyridi ◽

E Topakas ◽

N Aligiannis ◽

P Christakopoulos ◽

AL Skaltsounis ◽

...

Keyword(s):

Biomass Production ◽

Submerged Culture ◽

Bioactive Compound ◽

Medicinal Mushroom ◽

Ganoderma Australe

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Synthesis and Breakdown of the Universal Precursors to Biological Metabolism Promoted by Ferrous Iron

10.26434/chemrxiv.7178930.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Kamila B. Muchowska ◽

Sreejith Jayasree VARMA ◽

Joseph Moran

Keyword(s):

Amino Acids ◽

Chemical Reaction ◽

Metabolic Pathways ◽

Ferrous Iron ◽

Reaction Network ◽

Tca Cycle ◽

Chemical Reaction Network ◽

Metabolic Precursors ◽

Tca Cycle Intermediates

How core biological metabolism initiated and why it uses the intermediates, reactions and pathways that it does remains unclear. Life builds its molecules from CO2 and breaks them down to CO2 again through the intermediacy of just five metabolites that act as the hubs of biochemistry. Here, we describe a purely chemical reaction network promoted by Fe2+ in which aqueous pyruvate and glyoxylate, two products of abiotic CO2 reduction, build up nine of the eleven TCA cycle intermediates, including all five universal metabolic precursors. The intermediates simultaneously break down to CO2 in a life-like regime resembling biological anabolism and catabolism. Introduction of hydroxylamine and Fe0 produces four biological amino acids. The network significantly overlaps the TCA/rTCA and glyoxylate cycles and may represent a prebiotic precursor to these core metabolic pathways.

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Ethnomedicinal uses, Phytochemistry and Pharmacological Aspects of the Genus Berberis Linn: A Comprehensive Review

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999201102141206 ◽

2020 ◽

Vol 23 ◽

Author(s):

Roohi Mohi-ud-din ◽

Reyaz Hassan Mir ◽

Prince Ahad Mir ◽

Saeema Farooq ◽

Syed Naiem Raza ◽

...

Keyword(s):

Chemical Constituents ◽

Pharmacological Activities ◽

Traditional Use ◽

Comprehensive Review ◽

Wide Range ◽

Anti Cancer ◽

Comprehensive Survey ◽

Ethnomedicinal Uses

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. Objective: The present review is focussed to summarize and collect the updated review of information of Genus Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory both in vitro & in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.

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Indonesian Law

10.1093/oso/9780199677740.001.0001 ◽

2018 ◽

Cited By ~ 1

Author(s):

Tim Lindsey ◽

Simon Butt

Keyword(s):

Environmental Law ◽

Customary Law ◽

State Agencies ◽

Court Decisions ◽

Banking Competition ◽

Inheritance System ◽

Wide Range ◽

Forest Law ◽

Comprehensive Survey ◽

The Law

This book explains Indonesia’s complex legal system and how it works. Covering a wide range of substantive topics from public to private law, including commercial, criminal, and constitutional law, it is the first comprehensive survey of Indonesian law in English. Offering clear answers to practical problems of current law, each chapter sets out relevant laws and leading court decisions, accompanied by an explanation of how the law works in practice, with an analytical critique. The book begins with an account of Indonesia’s Constitution and the key state agencies, before moving to the lawmaking process, decentralization, the judicial system and court procedure, and the legal profession (advocates, notaries, and legal aid). Part II covers traditional customary law (adat), land law, and environmental law, including forest law. Part III focuses on criminal law and procedure, including investigation, arrest, trial, sentencing, and appeals. It also covers human rights law and the law on corruption. Part IV deals with civil law, and covers civil liability, contracts, companies and other business vehicles, labour, foreign investment, taxation, insolvency, banking, competition, and media law. The book concludes in Part V with an account of Indonesia’s complex family law and inheritance system for both Muslims and non-Muslims. The book has an extensive glossary of legal terms, and detailed tables of legislation and court decisions, designed as unique resources for lawyers, policymakers, and researchers.

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The Role of Cell Metabolism in Innate Immune Memory

Journal of Innate Immunity ◽

10.1159/000512280 ◽

2020 ◽

pp. 1-9

Author(s):

Anaisa Valido Ferreira ◽

Jorge Domiguéz-Andrés ◽

Mihai Gheorghe Netea

Keyword(s):

Metabolic Pathways ◽

Tricarboxylic Acid Cycle ◽

Cell Metabolism ◽

Innate Immune ◽

Immune Memory ◽

Functional Changes ◽

Trained Immunity ◽

Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined trained immunity or innate immune memory, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

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The Metabolic Fates of Pyruvate in Normal and Neoplastic Cells

Cells ◽

10.3390/cells10040762 ◽

2021 ◽

Vol 10 (4) ◽

pp. 762

Author(s):

Edward V. Prochownik ◽

Huabo Wang

Keyword(s):

Metabolic Pathways ◽

Redox State ◽

Pyruvate Dehydrogenase Complex ◽

Tca Cycle ◽

Vascular Supply ◽

Extrinsic Factors ◽

The Tca Cycle ◽

Initial Substrate ◽

Numerous Cell ◽

Bio Synthesis

Pyruvate occupies a central metabolic node by virtue of its position at the crossroads of glycolysis and the tricarboxylic acid (TCA) cycle and its production and fate being governed by numerous cell-intrinsic and extrinsic factors. The former includes the cell’s type, redox state, ATP content, metabolic requirements and the activities of other metabolic pathways. The latter include the extracellular oxygen concentration, pH and nutrient levels, which are in turn governed by the vascular supply. Within this context, we discuss the six pathways that influence pyruvate content and utilization: 1. The lactate dehydrogenase pathway that either converts excess pyruvate to lactate or that regenerates pyruvate from lactate for use as a fuel or biosynthetic substrate; 2. The alanine pathway that generates alanine and other amino acids; 3. The pyruvate dehydrogenase complex pathway that provides acetyl-CoA, the TCA cycle’s initial substrate; 4. The pyruvate carboxylase reaction that anaplerotically supplies oxaloacetate; 5. The malic enzyme pathway that also links glycolysis and the TCA cycle and generates NADPH to support lipid bio-synthesis; and 6. The acetate bio-synthetic pathway that converts pyruvate directly to acetate. The review discusses the mechanisms controlling these pathways, how they cross-talk and how they cooperate and are regulated to maximize growth and achieve metabolic and energetic harmony.

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Itaconate Alters Succinate and Coenzyme A Metabolism via Inhibition of Mitochondrial Complex II and Methylmalonyl-CoA Mutase

Metabolites ◽

10.3390/metabo11020117 ◽

2021 ◽

Vol 11 (2) ◽

pp. 117

Author(s):

Thekla Cordes ◽

Christian M. Metallo

Keyword(s):

Amino Acid ◽

Metabolic Pathways ◽

Mammalian Cells ◽

Coenzyme A ◽

Cultured Cells ◽

Tca Cycle ◽

Regulatory Function ◽

Reversible Inhibitor ◽

Complex Ii ◽

Branched Chain

Itaconate is a small molecule metabolite that is endogenously produced by cis-aconitate decarboxylase-1 (ACOD1) in mammalian cells and influences numerous cellular processes. The metabolic consequences of itaconate in cells are diverse and contribute to its regulatory function. Here, we have applied isotope tracing and mass spectrometry approaches to explore how itaconate impacts various metabolic pathways in cultured cells. Itaconate is a competitive and reversible inhibitor of Complex II/succinate dehydrogenase (SDH) that alters tricarboxylic acid (TCA) cycle metabolism leading to succinate accumulation. Upon activation with coenzyme A (CoA), itaconyl-CoA inhibits adenosylcobalamin-mediated methylmalonyl-CoA (MUT) activity and, thus, indirectly impacts branched-chain amino acid (BCAA) metabolism and fatty acid diversity. Itaconate, therefore, alters the balance of CoA species in mitochondria through its impacts on TCA, amino acid, vitamin B12, and CoA metabolism. Our results highlight the diverse metabolic pathways regulated by itaconate and provide a roadmap to link these metabolites to potential downstream biological functions.

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Recent Advances in Unmanned Aerial Vehicle Forest Remote Sensing—A Systematic Review. Part I: A General Framework

Forests ◽

10.3390/f12030327 ◽

2021 ◽

Vol 12 (3) ◽

pp. 327 ◽

Cited By ~ 1

Author(s):

Riccardo Dainelli ◽

Piero Toscano ◽

Salvatore Filippo Di Gennaro ◽

Alessandro Matese

Keyword(s):

Remote Sensing ◽

Unmanned Aerial Vehicle ◽

Relevant Information ◽

Forest Monitoring ◽

Machine Learning Techniques ◽

Planted Forests ◽

Systematic Analysis ◽

Aerial Photogrammetry ◽

Wide Range ◽

Aerial Vehicle

Natural, semi-natural, and planted forests are a key asset worldwide, providing a broad range of positive externalities. For sustainable forest planning and management, remote sensing (RS) platforms are rapidly going mainstream. In a framework where scientific production is growing exponentially, a systematic analysis of unmanned aerial vehicle (UAV)-based forestry research papers is of paramount importance to understand trends, overlaps and gaps. The present review is organized into two parts (Part I and Part II). Part II inspects specific technical issues regarding the application of UAV-RS in forestry, together with the pros and cons of different UAV solutions and activities where additional effort is needed, such as the technology transfer. Part I systematically analyzes and discusses general aspects of applying UAV in natural, semi-natural and artificial forestry ecosystems in the recent peer-reviewed literature (2018–mid-2020). The specific goals are threefold: (i) create a carefully selected bibliographic dataset that other researchers can draw on for their scientific works; (ii) analyze general and recent trends in RS forest monitoring (iii) reveal gaps in the general research framework where an additional activity is needed. Through double-step filtering of research items found in the Web of Science search engine, the study gathers and analyzes a comprehensive dataset (226 articles). Papers have been categorized into six main topics, and the relevant information has been subsequently extracted. The strong points emerging from this study concern the wide range of topics in the forestry sector and in particular the retrieval of tree inventory parameters often through Digital Aerial Photogrammetry (DAP), RGB sensors, and machine learning techniques. Nevertheless, challenges still exist regarding the promotion of UAV-RS in specific parts of the world, mostly in the tropical and equatorial forests. Much additional research is required for the full exploitation of hyperspectral sensors and for planning long-term monitoring.

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