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Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth

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The Innovation 2024年第2期5卷 107-114页

作者： Johan Gustafsson Fariba Roshanzamir Anders Hagnestål Sagar M.Patel oseeyi I.Daudu Donald F.Becker Jonathan L.Robinson jens nielsen Department of Life Sciences Chalmers University of TechnologySE-41296 GothenburgSweden Hagnesia AB SE-43854 HindåsSweden Department of Biochemistry and Redox Biology center University of Nebraska-LincolnLincolnNE 68588USA BioInnovation Institute DK2200 CopenhagenDenmark

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation,but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in ***-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell ***,we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion *** addition,we developed an approach to efficiently apply enzyme usage constraints in a comprehensive metabolic model of human *** combined modeling reproduced severe hypoxic conditions and the Warburg effect,and we found that limitations in enzymatic capacity contribute to cancer cells’preferential use of glutamine as a substrate to the citric acid ***,we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites useful for the cancer *** identified over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated fibroblasts,but when limiting to metabolites previously identified to participate in such collaboration,no growth advantage was *** work highlights the importance of enzymatic capacity limitations for cell behaviors and exemplifies the utility of enzyme-constrained models for accurate prediction of metabolism in cells and tumor microenvironments.

关键词： metabolism effect limitations

Steroidal scaffold decorations in Solanum alkaloid biosynthesis

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Molecular Plant 2024年第8期17卷 1236-1254页

作者： Rosalind Lucier Mohamed o.Kamileen Yoko Nakamura Sofiia Serediuk Ranjit Barbole jens Wurlitzer Maritta Kunert Sarah Heinicke Sarah E.o'connor Prashant D.Sonawane Department of Natural Product Biosynthesis Max Planck Institute for Chemical Ecology07745 JenaGermany Research Group Biosynthesis and NMR Max Planck Institute for Chemical Ecology07745 JenaGermany Biochemical Sciences Division CSIR-National Chemical LaboratoryPune 411008MaharashtraIndia

Steroidal glycoalkaloids(SGAs)are specialized metabolites produced by hundreds of Solanum species,including important vegetable crops such as tomato,potato,and *** it has been known that SGAs play important roles in defense in plants and“anti-nutritional"effects(e.g.,toxicity and bitterness)to humans,many of these molecules have documented anti-cancer,anti-microbial,antiinflammatory,anti-viral,and anti-pyretic *** these,α-solasonine andα-solamargine isolated from black nightshade(Solanum nigrum)are reported to have potent anti-tumor,anti-proliferative,and anti-inflammatory ***,α-solasonine andα-solamargine,along with the core steroidal aglycone solasodine,are the most widespread SGAs produced among the Solanum ***,it is still unknown how plants synthesize these bioactive steroidal *** comparative metabolomictranscriptome-guided approach,biosynthetic logic,combinatorial expression in Nicotiana benthamiana,and functional recombinant enzyme assays,here we report the discovery of 12 enzymes from *** that converts the starting cholesterol precursorto solasodine aglycone,and the downstreamα-solasonine,α-solamargine,and malonyl-solamargine SGA *** further identified six enzymes from cultivated eggplant that catalyze the production ofα-solasonine,α-solamargine,and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation *** work provides the gene tool box and platform for engineering the production of high-value,steroidal bioactive molecules inheterologoushosts usingsyntheticbiology.

关键词： steroidal glycoalkaloids Solanum biosynthetic pathway α-solamargine malonyl-solamargine specialized metabolites

Non-linear dynamic state-space network modeling for decoding neurodegeneration

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Neural Regeneration Research 2024年第9期19卷 1879-1880页

作者： Venkata c.chirumamilla chi Wang Ip Martin Reich Robert Peach jens Volkmann Bahman Nasseroleslami Muthuraman Muthuraman Prenatal Pediatrics Institute Children’s National HospitalWashingtonDCUSA Neural Engineering with Signal Analytics and Artificial Intelligence Department of NeurologyUniversity of WürzburgWürzburgGermany Academic Unit of Neurology Trinity Biomedical Sciences InstituteTrinity College DublinUniversity of DublinDublinIreland

Neurodegenerative disorders represent a pervasive global health challenge,yet therapeutic options remain conspicuously *** disorders are inherently dynamic processes within the central nervous system,unfolding across distinct sub-stages:initial structural neuronal alterations(sub-stage 1),functional impairment(sub-stage 2),and culminating in neuronal death(sub-stage 3).

关键词： alterations impairment dynamic

Development of fungal cell factories for the production of secondary metabolites:Linking genomics and metabolism

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Synthetic and Systems Biotechnology 2017年第1期2卷 5-12页

作者： jens christian nielsen jens nielsen chalmers University of Technology Kemivagen 10Sweden

The genomic era has revolutionized research on secondary metabolites and bioinformatics methods have in recent years revived the antibiotic discovery process after decades with only few new active molecules being *** computational tools are driven by genomics and metabolomics analysis,and enables rapid identification of novel secondary *** translate this increased discovery rate into industrial exploitation,it is necessary to integrate secondary metabolite pathways in the metabolic engineering *** this review,we will describe the novel advances in discovery of secondary metabolites produced by filamentous fungi,highlight the utilization of genome-scale metabolic models(GEMs)in the design of fungal cell factories for the production of secondary metabolites and review strategies for optimizing secondary metabolite production through the construction of high yielding platform cell factories.

关键词： Secondary metabolism Fungi Biosynthetic gene clusters Genome mining Metabolic modeling cell factories

Pressure pain sensitivity: A new stress measure in children and adolescents with type 1 diabetes?

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World Journal of clinical Pediatrics 2024年第1期13卷 150-154页

作者： Annemarie cecilie Grauslund Emilie Bundgaard Lindkvist Steffen Ullitz Thorsen Søren Ballegaard jens Faber Jannet Svensson Anna Korsgaard Berg Department of Pediatrics Herlev and Gentofte HospitalHerlev 2730Denmark copenhagen University Hospital Steno Diabetes Center CopenhagenHerlev 2730Denmark Department of clinical Immunology RigshospitaletUniversity of CopenhagenCopenhagen 2100Denmark Department of Endocrinology Herlev and Gentofte HospitalHerlev 2730Denmark Department of clinical Medicine Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen 2200Denmark

Type 1 diabetes(T1D)is associated with general-and diabetes-specific stress which has multiple adverse *** measuring stress is of great *** algometer measuring pressure pain sensitivity(PPS)has been shown to correlate to certain stress measures in ***,it has never been investigated in children and *** aim of our study was to examine associations between PPS and glycated hemoglobin(HbA1c),salivary cortisol and two questionnaires as well as to identify whether the algometer can be used as a clinical tool among children and adolescents with ***-three participants aged 6-18 years and diagnosed with T1D were included in this study with data from two study *** cortisol,PPS and questionnaires were collected,measured,and answered on ***1c was collected from medical *** found correlations between PPS and HbA1c(rho=0.35,P=0.046),cortisol(rho=-0.25,P=0.02)and Perceived Stress Scale(rho=-0.44,P=0.02)in different subgroups based on *** scored higher in PPS than females(Pound PPS to be correlated to HbA1c but otherwise inconsistent in *** PPS values indicated either measurement difficulties or hypersensibility towards pain.

关键词： Stress children and adolescents Type 1 diabetes Autonomic dysfunction

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利用择形分子筛异构化亚甲基二苯胺

chinese Journal of catalysis 2024年第7期62卷 124-130页

作者： Sam Van Minnebruggen Ka Yan cheung Trees De Baerdemaeker Niels Van Velthoven Matthias Degelin Galahad o’Rourke Hiroto Toyoda Andree Iemhoff Imke Muller Andrei-Nicolae Parvulescu Torsten Mattke jens Ferbitz 吴勤明肖丰收 Toshiyuki Yokoi Nils Bottke Dirk De Vos 巴斯夫股份有限公司膜分离、吸附、催化和光谱学可持续解决方案中心(cMAcS) 比利时巴斯夫股份有限公司研究组德国东京工业大学纳米空间催化研究所横滨日本浙江大学化学系浙江杭州310028

亚甲基二苯胺(MDA)被广泛用作生产聚氨酯和聚异氰脲酸酯的中间体.然而,当前MDA的生产工艺在控制(4,4’/(2,4’+2,2’))异构体比例方面还存在局限.其中,4,4’-MDA被认为是最有价值的异构体.尽管2,4'-MDA在市场上也有一定的需求,但如果能... 详细信息

亚甲基二苯胺(MDA)被广泛用作生产聚氨酯和聚异氰脲酸酯的中间体.然而,当前MDA的生产工艺在控制(4,4’/(2,4’+2,2’))异构体比例方面还存在局限.其中,4,4’-MDA被认为是最有价值的异构体.尽管2,4'-MDA在市场上也有一定的需求,但如果能将其有效地转化为4,4'-MDA,将能显著提升其附加值.本文在使用苯胺的条件下,利用β分子筛等催化剂,通过双分子机制,可以选择性地将2,4'-MDA异构化为4,4'-MDA.尽管实验显示,多种酸性沸石具有较高的异构化活性,但McM-68(具有MSE拓扑结构)的催化性能尤为出色,它不仅展现出高异构化活性,而且具有很好的选择性.McM-68主要催化2,4'-MDA异构化为4,4'-MDA,而2,2'-MDA和低聚物的形成则可以忽略不计.本文还深入探讨了该择形作用的原因,并详细研究了酸位置在MSE分子筛孔道限制中的关键作用.

关键词：铝分布多相催化异构化亚甲基二苯胺聚氨酯择形

Editorial for “Biointelligent manufacturing in Memorium of Arnold (Arny) L. Demain”

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Synthetic and Systems Biotechnology 2022年第4期7卷 1185-1186页

作者： Qiang Gao jens nielsen Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education College of BiotechnologyTianjin University of Science and TechnologyTianjin300457China BioInnovation Institute Ole Maaloes Vej 3Copenhagen NDK2200Denmark

Biointelligent manufacturing is currently at the center of industrial *** biotechnology has historic roots dating thousand years back where microbial fermentation was used to preserve foods,make bread and fermented drinks,but has risen to a modern *** of the development into a modern industry was driven initially by production of antibiotics and later by production of food and feed *** this development,the late MIT emeritus Professor Arnold(Arny)Lester Demain was one of the drivers and is considered one of the founders of industrial *** research founds wide applications and he stands as one of the giants in the field of industrial microbiology and biotechnology[1-7].

关键词： Arnold biotechnology initially

Expression of fungal biosynthetic gene clusters in S. cerevisiae for natural product discovery

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Synthetic and Systems Biotechnology 2021年第1期6卷 20-22页

作者： Zihe Liu Zhenquan Lin jens nielsen college of Life Science and Technology Beijing Advanced Innovation Center for Soft Matter Science and EngineeringBeijing University of Chemical Technology100029BeijingChina Department of Biology and Biological Engineering Chalmers University of TechnologySE41296GothenburgSweden Novo Nordisk Foundation center for Biosustainability Technical University of DenmarkDK2800LyngbyDenmark BioInnovation Institute Ole Maaløes Vej 3DK2200Copenhagen NDenmark

Fungi are well known for production of antibiotics and other bioactive secondary metabolites,that can be served as pharmaceuticals,therapeutic agents and industrially useful ***,compared with the characterization of prokaryotic biosynthetic gene clusters(BGcs),less attention has been paid to evaluate fungal *** is partially because heterologous expression of eukaryotic gene constructs often requires replacement of original promoters and terminators,as well as removal of intron sequences,and this substantially slow down the workflow in natural product *** is therefore of interest to investigate the possibility and effectiveness of heterologous expression and library screening of intact BGcs without refactoring in industrial friendly microbial cell factories,such as the yeast Saccharomyces ***,we discuss the importance of developing new research directions on library screening of fungal BGcs in yeast without refactoring,followed by outlooking prominent opportunities and challenges for future advancement.

关键词： Natural product discovery cross-species engineering Spliceosome High-throughput BGc cloning Synthetic biology Yeast

Rewiring regulation on respiro-fermentative metabolism relieved crabtree effects in Saccharomyces cerevisiae

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Synthetic and Systems Biotechnology 2022年第4期7卷 1034-1043页

作者： Yiming Zhang Mo Su Zheng Wang jens nielsen Zihe Liu Beijing Advanced Innovation center for Soft Matter Science and Engineering College of Life Science and TechnologyBeijing University of Chemical Technology100029BeijingChina Bloomage Biotechnolgy co LTD250000JinanChina Department of Biology and Biological Engineering Chalmers University of TechnologySE296GothenburgSweden BioInnovation Institute Ole Maaløes Vej 3DK2200Copenhagen NDenmark

The respiro-fermentative metabolism in the yeast Saccharomyces cerevisiae,also called the crabtree effect,results in lower energy efficiency and biomass yield which can impact yields of chemicals to be produced using this cell *** it can be engineered to become crabtree negative,the slow growth and glucose consumption rate limit its industrial *** the crabtree effect in yeast can be alleviated by engineering the transcription factor Mth1 involved in glucose signaling and a subunit of the RNA polymerase II mediator complex *** was found that the mutant with the MTH1A81D&MED2*432Y allele could grow in glucose rich medium with a specific growth rate of 0.30 h^(-1),an ethanol yield of 0.10 g g^(-1),and a biomass yield of 0.21 g g^(-1),compared with a specific growth rate of 0.40 h^(-1),an ethanol yield of 0.46 g g^(-1),and a biomass yield of 0.11 g g^(-1) in the wild-type strain *** *** analysis revealed significant downregulation of the glycolytic process,as well as the upregulation of the TcA cycle and the electron transfer *** expression changes of several reporter transcription factors were also identified,which might explain the higher energy efficiencies in the engineered *** further demonstrated the potential of the engineered strain with the production of 3-hydroxypropionic acid at a titer of 2.04 g L^(-1),i.e.,5.4-fold higher than that of a reference strain,indicating that the alleviated glucose repression could enhance the supply of mitochondrial *** results suggested that the engineered strain could be used as an efficient cell factory for mitochondrial production of acetyl-coA derived chemicals.

关键词： Respiro-fermentation crabtree effect Saccharomyces cerevisiae 3-Hydroxypropionic acid