Affiliation: Chalmers University of Technology
- Shoaie S, Ghaffari P, Kovatcheva Datchary P, Mardinoglu A, Sen P, Pujos Guillot E, et al. Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome. Cell Metab. 2015;22:320-31 pubmed publisher..Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention. ..
- Liu Q, Yu T, Campbell K, Nielsen J, Chen Y. Modular Pathway Rewiring of Yeast for Amino Acid Production. Methods Enzymol. 2018;608:417-439 pubmed publisher..Additionally, detailed protocols for in vitro module construction and CRISPR/Cas-mediated pathway assembly are provided. ..
- Kumar M, Ji B, Babaei P, Das P, Lappa D, Ramakrishnan G, et al. Gut microbiota dysbiosis is associated with malnutrition and reduced plasma amino acid levels: Lessons from genome-scale metabolic modeling. Metab Eng. 2018;49:128-142 pubmed publisher..Our analyses provide a framework for future efforts towards further characterization of gut microbial metabolic capabilities and their contribution to malnutrition. ..
- Krivoruchko A, Nielsen J. Production of natural products through metabolic engineering of Saccharomyces cerevisiae. Curr Opin Biotechnol. 2015;35:7-15 pubmed publisher..Key achievements in the production of different isoprenoids, aromatics and polyketides are presented and the metabolic engineering strategies underlying these accomplishments are discussed. ..
- VÃ¤remo L, Scheele C, Broholm C, Mardinoglu A, Kampf C, Asplund A, et al. Proteome- and transcriptome-driven reconstruction of the human myocyte metabolic network and its use for identification of markers for diabetes. Cell Rep. 2015;11:921-933 pubmed publisher..Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D. ..
- Nielsen J, Larsson C, van Maris A, Pronk J. Metabolic engineering of yeast for production of fuels and chemicals. Curr Opin Biotechnol. 2013;24:398-404 pubmed publisher..Here we review recent scientific progress in metabolic engineering of S. cerevisiae for the production of bioethanol, advanced biofuels, and chemicals. ..
- Yu T, Zhou Y, Huang M, Liu Q, Pereira R, David F, et al. Reprogramming Yeast Metabolism from Alcoholic Fermentation to Lipogenesis. Cell. 2018;174:1549-1558.e14 pubmed publisher..Genome sequencing of evolved strains showed that pyruvate kinase mutations were essential for this phenotype. ..
- Nilsson A, Haanstra J, Teusink B, Nielsen J. Metabolite Depletion Affects Flux Profiling of Cell Lines. Trends Biochem Sci. 2018;43:395-397 pubmed publisher..Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation. ..
- Rodríguez A, Kildegaard K, Li M, Borodina I, Nielsen J. Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis. Metab Eng. 2015;31:181-8 pubmed publisher..The developed S. cerevisiae strain represents an attractive platform host for production of p-coumaric-acid derived secondary metabolites, such as flavonoids, polyphenols, and polyketides. ..
- Krivoruchko A, Zhang Y, Siewers V, Chen Y, Nielsen J. Microbial acetyl-CoA metabolism and metabolic engineering. Metab Eng. 2015;28:28-42 pubmed publisher..cerevisiae and E. coli), with an emphasis on reactions involved in the production and consumption of acetyl-CoA. In addition, we review various strategies that have been used to increase acetyl-CoA production in these microbes. ..
- SÃ¡nchez B, Nielsen J. Genome scale models of yeast: towards standardized evaluation and consistent omic integration. Integr Biol (Camb). 2015;7:846-58 pubmed publisher..Relevant conclusions and current challenges for both GEM evaluation and omic integration are highlighted. ..
- Zhang Y, Dai Z, Krivoruchko A, Chen Y, Siewers V, Nielsen J. Functional pyruvate formate lyase pathway expressed with two different electron donors in Saccharomyces cerevisiae at aerobic growth. FEMS Yeast Res. 2015;15:fov024 pubmed publisher..Among the two electron donors reduced flavodoxin was found to be a better electron donor than reduced ferredoxin. ..
- Dai Z, Nielsen J. Advancing metabolic engineering through systems biology of industrial microorganisms. Curr Opin Biotechnol. 2015;36:8-15 pubmed publisher..Finally, we present some perspectives of systems biology for advancing metabolic engineering further. ..
- Mardinoglu A, Nielsen J. New paradigms for metabolic modeling of human cells. Curr Opin Biotechnol. 2015;34:91-7 pubmed publisher..Finally, challenges in integration of cell/tissue models for simulation of whole body functions as well as integration of GEMs with other biological networks for generating complete cell/tissue models are presented. ..
- Nielsen J. Synthetic biology for engineering acetyl coenzyme A metabolism in yeast. MBio. 2014;5:e02153 pubmed publisher..Here the perspective of generating yeast platform strains that have such properties is discussed in the context of a major breakthrough with expression of a functional pyruvate dehydrogenase complex in the cytosol. ..
- Fletcher E, Feizi A, Kim S, Siewers V, Nielsen J. RNA-seq analysis of Pichia anomala reveals important mechanisms required for survival at low pH. Microb Cell Fact. 2015;14:143 pubmed publisher..anomala which was previously unknown. Ultimately, this is a step towards developing non-conventional yeasts such as P. anomala for the production of industrially relevant chemicals under low pH conditions. ..
- Liu L, Zhang Y, Liu Z, Petranovic D, Nielsen J. Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae. FEMS Yeast Res. 2015;15: pubmed publisher..Based on the genome-wide transcriptional response, we specifically focused on the effect of UPC2 upregulation on protein production and suggested a possible mechanistic explanation. ..
- Garcia Albornoz M, Nielsen J. Finding directionality and gene-disease predictions in disease associations. BMC Syst Biol. 2015;9:35 pubmed publisher..However, the gene-disease-pathway associations can be used for prediction of new gene-disease interactions that will be useful in drug discovery and therapeutic applications. ..
- Wei Y, Bergenholm D, Gossing M, Siewers V, Nielsen J. Expression of cocoa genes in Saccharomyces cerevisiae improves cocoa butter production. Microb Cell Fact. 2018;17:11 pubmed publisher..cerevisiae, showing that metabolic engineering of yeast for cocoa butter production can be realized by manipulating the key enzymes GPAT, LPAT and DGAT in the TAG biosynthetic pathway. ..
- Caspeta L, Chen Y, Ghiaci P, Feizi A, Buskov S, HallstrÃ¶m B, et al. Biofuels. Altered sterol composition renders yeast thermotolerant. Science. 2014;346:75-8 pubmed publisher..Additionally, large chromosome III rearrangements and mutations in genes associated with DNA damage and respiration were found, but contributed less to the thermotolerant phenotype. ..
- Fletcher E, Feizi A, Bisschops M, HallstrÃ¶m B, Khoomrung S, Siewers V, et al. Evolutionary engineering reveals divergent paths when yeast is adapted to different acidic environments. Metab Eng. 2017;39:19-28 pubmed publisher..Therefore, different strategies are required for a rational design of low pH tolerant strains depending on the acid of interest. ..
- Shi S, Ji H, Siewers V, Nielsen J. Improved production of fatty acids by Saccharomyces cerevisiae through screening a cDNA library from the oleaginous yeast Yarrowia lipolytica. FEMS Yeast Res. 2016;16:fov108 pubmed publisher..Our findings not only provide a novel method for high-throughput evaluation of the content of free FAs, but also give new insight into how enzymes from Y. lipolytica may increase the production of fatty acids in S. cerevisiae. ..
- de Jong B, Siewers V, Nielsen J. Physiological and transcriptional characterization of Saccharomyces cerevisiae engineered for production of fatty acid ethyl esters. FEMS Yeast Res. 2016;16:fov105 pubmed publisher..In conclusion, our analysis clearly shows that engineering of fatty acid biosynthesis results in transcriptional reprogramming and has a significant effect on overall cellular metabolism. ..
- Otero J, Vongsangnak W, Asadollahi M, Olivares Hernandes R, Maury J, Farinelli L, et al. Whole genome sequencing of Saccharomyces cerevisiae: from genotype to phenotype for improved metabolic engineering applications. BMC Genomics. 2010;11:723 pubmed publisher..The genome sequence, annotation, and a SNP viewer of CEN.PK113-7D are deposited at http://www.sysbio.se/cenpk. ..
- Irani Z, Kerkhoven E, Shojaosadati S, Nielsen J. Genome-scale metabolic model of Pichia pastoris with native and humanized glycosylation of recombinant proteins. Biotechnol Bioeng. 2016;113:961-9 pubmed publisher..The model represents a step towards a more complete description of protein production in P. pastoris, which is required for using these models to understand and optimize protein production processes. ..
- Chen Y, Nielsen J. Biobased organic acids production by metabolically engineered microorganisms. Curr Opin Biotechnol. 2016;37:165-172 pubmed publisher..Also, the key limitations and challenges in microbial organic acids production are discussed. ..
- Gatto F, Nielsen J. Systematic analysis of overall survival and interactions between tumor mutations and drug treatment. J Hematol Oncol. 2016;9:15 pubmed publisher..Our results suggest infrequent instances of exceptional responses ascribable to tumor genomics yet corroborate the existence of an interaction of temozolomide with IDH1 mutations in lower-grade glioma. ..
- Ferreira R, David F, Nielsen J. Advancing biotechnology with CRISPR/Cas9: recent applications and patent landscape. J Ind Microbiol Biotechnol. 2018;45:467-480 pubmed publisher..Next, we detail the current status of the patent landscape, highlighting its exploitation through different companies, and conclude with future perspectives of this technology. ..
- Nilsson A, Nielsen J. Genome scale metabolic modeling of cancer. Metab Eng. 2017;43:103-112 pubmed publisher..GEMs have great potential for translational research on cancer and will therefore become of increasing importance in the future. ..
- Nilsson A, Nielsen J, Palsson B. Metabolic Models of Protein Allocation Call for the Kinetome. Cell Syst. 2017;5:538-541 pubmed publisher..Recently, many metabolic phenotypes have been explained by computer models that incorporate enzyme activity data. To move further, the scientific community needs to measure the kinetics of all enzymes in a systematic way. ..
- Lindskog C, LinnÃ© J, Fagerberg L, HallstrÃ¶m B, Sundberg C, Lindholm M, et al. The human cardiac and skeletal muscle proteomes defined by transcriptomics and antibody-based profiling. BMC Genomics. 2015;16:475 pubmed publisher..These proteins represent an interesting starting point for further functional analysis of their role in muscle biology and disease. ..
- Kerkhoven E, Lahtvee P, Nielsen J. Applications of computational modeling in metabolic engineering of yeast. FEMS Yeast Res. 2015;15:1-13 pubmed..This review will give an overview about models available for metabolic engineering of yeast and discusses their applications. ..
- Lee S, Mardinoglu A, Zhang C, Lee D, Nielsen J. Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis. Nucleic Acids Res. 2016;44:5529-39 pubmed publisher..Based on our analysis we suggest signaling hub genes governing overall catabolic or anabolic pathways, as novel drug targets for treatment of HCC that involves lipid anomalies. ..
- Robinson J, Nielsen J. Integrative analysis of human omics data using biomolecular networks. Mol Biosyst. 2016;12:2953-64 pubmed publisher..As the volume and resolution of high-throughput omics data continue to grow, integrative network-based analyses are expected to play an increasingly important role in their interpretation. ..
- Andersen M, Giese M, de Vries R, Nielsen J. Mapping the polysaccharide degradation potential of Aspergillus niger. BMC Genomics. 2012;13:313 pubmed..In plant-biomass degrading fungi, these enzymes are regulated and released by complex regulatory structures. In this study, we present a methodology for evaluating the potential of a given fungus for polysaccharide degradation...
- Gatto F, Schulze A, Nielsen J. Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics. Cell Rep. 2016;16:878-95 pubmed publisher..These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network. ..
- Liu G, Bergenholm D, Nielsen J. Genome-Wide Mapping of Binding Sites Reveals Multiple Biological Functions of the Transcription Factor Cst6p in Saccharomyces cerevisiae. MBio. 2016;7: pubmed publisher..These results provide deeper understanding of the function of the dynamic transcriptional regulatory network in S. cerevisiae. ..
- Hu Y, Zhou Y, Bao J, Huang L, Nielsen J, Krivoruchko A. Metabolic engineering of Saccharomyces cerevisiae for production of germacrene A, a precursor of beta-elemene. J Ind Microbiol Biotechnol. 2017;44:1065-1072 pubmed publisher..These results provide a basis for creating an efficient route for further industrial application re-placing the traditional extraction of beta-elemene from plant sources. ..
- Rodríguez A, Chen Y, Khoomrung S, Ozdemir E, Borodina I, Nielsen J. Comparison of the metabolic response to over-production of p-coumaric acid in two yeast strains. Metab Eng. 2017;44:265-272 pubmed publisher..PK high-producing strain. This study demonstrates the importance of transporters in the engineering of cell factories for production of small molecules. ..
- Bao J, Huang M, Petranovic D, Nielsen J. Moderate Expression of SEC16 Increases Protein Secretion by Saccharomyces cerevisiae. Appl Environ Microbiol. 2017;83: pubmed publisher..cerevisiae This new strategy can be combined with other targets to engineer cell factories to efficiently produce protein in the future. ..
- Campbell K, Xia J, Nielsen J. The Impact of Systems Biology on Bioprocessing. Trends Biotechnol. 2017;35:1156-1168 pubmed publisher..We discuss here the current impact of systems biology and challenges of closing the gap between bioprocessing and more traditional methods of chemical production. ..
- Wang G, Huang M, Nielsen J. Exploring the potential of Saccharomyces cerevisiae for biopharmaceutical protein production. Curr Opin Biotechnol. 2017;48:77-84 pubmed publisher..Here we review advances in systems biology and metabolic engineering of yeast for improving recombinant protein production. ..
- Huang M, Bao J, Hallström B, Petranovic D, Nielsen J. Efficient protein production by yeast requires global tuning of metabolism. Nat Commun. 2017;8:1131 pubmed publisher..Our findings provide increased understanding of which cellular regulations and pathways are associated with efficient protein secretion. ..
- ..Finally, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed. ..
- Teixeira P, Ferreira R, Zhou Y, Siewers V, Nielsen J. Dynamic regulation of fatty acid pools for improved production of fatty alcohols in Saccharomyces cerevisiae. Microb Cell Fact. 2017;16:45 pubmed publisher..The study also provides knowledge of a key point of fatty acid regulation and homeostasis, which can be used for future design of cells factories for fatty acid-derived chemicals. ..
- Nielsen J. Systems Biology of Metabolism: A Driver for Developing Personalized and Precision Medicine. Cell Metab. 2017;25:572-579 pubmed publisher..It will be illustrated how the concept of genome-scale metabolic models can be used for integrative analysis of big data with the objective of identifying novel biomarkers that are foundational for personalized and precision medicine. ..
- Wei Y, Gossing M, Bergenholm D, Siewers V, Nielsen J. Increasing cocoa butter-like lipid production of Saccharomyces cerevisiae by expression of selected cocoa genes. AMB Express. 2017;7:34 pubmed publisher..25-fold increased TAG content and 6.7-fold higher level of CBL compared with the control strain. In summary, CBL production by S. cerevisiae were increased through expressing selected cocoa genes potentially involved in CB biosynthesis. ..
- Tippmann S, Scalcinati G, Siewers V, Nielsen J. Production of farnesene and santalene by Saccharomyces cerevisiae using fed-batch cultivations with RQ-controlled feed. Biotechnol Bioeng. 2016;113:72-81 pubmed publisher..However, a reduction of the product yield on biomass by 50% could indicate a higher catalytic efficiency of the farnesene synthase. ..
- Chen Y, Zhang Y, Siewers V, Nielsen J. Ach1 is involved in shuttling mitochondrial acetyl units for cytosolic C2 provision in Saccharomyces cerevisiae lacking pyruvate decarboxylase. FEMS Yeast Res. 2015;15: pubmed publisher..These results will increase our fundamental understanding of intracellular transport of acetyl units, and also help to develop microbial cell factories for many kinds of acetyl-CoA derived products. ..
- Nielsen J. Systems biology of lipid metabolism: from yeast to human. FEBS Lett. 2009;583:3905-13 pubmed publisher..Hereby yeast systems biology can assist to improve our understanding of how lipid metabolism is regulated. ..
- Huang M, Joensson H, Nielsen J. High-Throughput Microfluidics for the Screening of Yeast Libraries. Methods Mol Biol. 2018;1671:307-317 pubmed publisher..This protocol can be adapted to screening by a range of other extracellular products from yeast or other hosts. ..
- Gatto F, Volpi N, Nilsson H, Nookaew I, Maruzzo M, Roma A, et al. Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma. Cell Rep. 2016;15:1822-36 pubmed publisher..In conclusion, coordinated regulation of GAG biosynthesis occurs in ccRCC, and non-invasive GAG profiling is suitable for mccRCC diagnosis. ..
- Kang M, Nielsen J. Biobased production of alkanes and alkenes through metabolic engineering of microorganisms. J Ind Microbiol Biotechnol. 2017;44:613-622 pubmed publisher..Here we review different pathways and involved enzymes for alkane and alkene production and discuss bottlenecks and possible solutions to accomplish industrial level production of these chemicals by microbial fermentation. ..
- Kocharin K, Nielsen J. Specific growth rate and substrate dependent polyhydroxybutyrate production in Saccharomyces cerevisiae. AMB Express. 2013;3:18 pubmed publisher..23 mg/L?·?h-1, at a dilution rate of 0.1 h-1. ..
- Väremo L, Gatto F, Nielsen J. Kiwi: a tool for integration and visualization of network topology and gene-set analysis. BMC Bioinformatics. 2014;15:408 pubmed publisher..Kiwi is available as a Python package at http://www.sysbio.se/kiwi and an online tool in the BioMet Toolbox at http://www.biomet-toolbox.org. ..
- Feizi A, Banaei Esfahani A, Nielsen J. HCSD: the human cancer secretome database. Database (Oxford). 2015;2015:bav051 pubmed publisher..The results are visualized in an explicit and interactive manner. An example of a result page includes annotations, cross references, cancer secretome data and secretory features for each identified protein. ..
- Kayıkçı Ö, Nielsen J. Glucose repression in Saccharomyces cerevisiae. FEMS Yeast Res. 2015;15: pubmed publisher..This review describes effects of glucose repression on yeast carbon metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and Snf1 signal transduction in establishment and relief of glucose repression. ..
- Fletcher E, Krivoruchko A, Nielsen J. Industrial systems biology and its impact on synthetic biology of yeast cell factories. Biotechnol Bioeng. 2016;113:1164-70 pubmed publisher..Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. Â© 2015 Wiley Periodicals, Inc. ..
- Lahtvee P, Sánchez B, Smialowska A, Kasvandik S, Elsemman I, Gatto F, et al. Absolute Quantification of Protein and mRNA Abundances Demonstrate Variability in Gene-Specific Translation Efficiency in Yeast. Cell Syst. 2017;4:495-504.e5 pubmed publisher..The present dataset represents a crucial expansion to the current resources for future studies on yeast physiology. ..
- Sen P, Mardinogulu A, Nielsen J. Selection of complementary foods based on optimal nutritional values. Sci Rep. 2017;7:5413 pubmed publisher..Key findings were that pork ham cured, fish pudding, and egg lean white induced better tissue growth, and quark with fruit, cheese quarg 45% and cheese cream 60% had similar lactose content as human milk. ..
- Wei Y, Siewers V, Nielsen J. Cocoa butter-like lipid production ability of non-oleaginous and oleaginous yeasts under nitrogen-limited culture conditions. Appl Microbiol Biotechnol. 2017;101:3577-3585 pubmed publisher..However, T. oleaginosus produced 27.8% potential POP and POS at levels of 378 mg TAGs/g dry cell weight, hinting that this yeast may have potential as a CBL production host after further metabolic engineering in future. ..
- Nielsen J. Production of biopharmaceutical proteins by yeast: advances through metabolic engineering. Bioengineered. 2013;4:207-11 pubmed publisher..The involvement of directed metabolic engineering through the integration of tools from genetic engineering, systems biology and mathematical modeling, is also discussed. ..
- Kang M, Zhou Y, Buijs N, Nielsen J. Functional screening of aldehyde decarbonylases for long-chain alkane production by Saccharomyces cerevisiae. Microb Cell Fact. 2017;16:74 pubmed publisher..cerevisiae. This work will be helpful to decide an AD candidate for alkane biosynthesis in S. cerevisiae and it will provide useful information for further investigation of AD enzymes with improved activities. ..
- Li M, Kildegaard K, Chen Y, Rodríguez A, Borodina I, Nielsen J. De novo production of resveratrol from glucose or ethanol by engineered Saccharomyces cerevisiae. Metab Eng. 2015;32:1-11 pubmed publisher..57 Â± 7.00 mg L(-1). Finally, fed-batch fermentation of the final strain with glucose or ethanol as carbon source resulted in a resveratrol titer of 415.65 and 531.41 mg L(-1), respectively. ..
- Väremo L, Henriksen T, Scheele C, Broholm C, Pedersen M, Uhlen M, et al. Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes. Genome Med. 2017;9:47 pubmed publisher..Our findings identify inherent characteristics in myocytes, as a memory of the in vivo phenotype, without the influence from a diabetic or obese extracellular environment, highlighting their importance in the development of T2D. ..
- Sánchez B, Zhang C, Nilsson A, Lahtvee P, Kerkhoven E, Nielsen J. Improving the phenotype predictions of a yeast genome-scale metabolic model by incorporating enzymatic constraints. Mol Syst Biol. 2017;13:935 pubmed publisher..Additionally, the model gives insight into the distribution of enzyme usage between and within metabolic pathways. The developed method and model are expected to increase the use of model-based design in metabolic engineering. ..