Forschungsbericht 2017



General methods and tools for systems and synthetic biology

Institut: V-1
Projektleitung: An-Ping Zeng
Stellvertretende Projektleitung: Uwe Jandt
Mitarbeiter/innen: Philipp Arbter
Lin Chen
Minliang Chen
Anna Gorte
Enrico Hans
Uwe Jandt
Chengwei Ma
Wael Sabra
Rebekka Schmitz (Geb. Brost)
Till Utesch
Wei Wang
Yujun Zhang
Laufzeit: 01.01.2007 — 31.12.2021
Finanzierung:Technische Universität Hamburg-Harburg (TUHH)
Internationalisierung:China, Costa Rica, Dänemark, Griechenland, Vereinigte Staaten

Stichworte

  • Stoffflussanalyse
  • synthetische Biologie
  • Systembiologie
  • Systems Biology

Publikationen

  • Bahnemann, J and Rajabi, N and Fuge, G and Barradas, O P and Müller, J and Pörtner, R and Zeng, A P: A New Integrated Lab-on-a-Chip System for Fast Dynamic Study of Mammalian Cells under Physiological Conditions in Bioreactor. Cells, 2(2): S. 349--360, 2013. , DOI: 10.3390/cells2020349
  • Liu, Yuan-Hua and Bi, Jing-Xiu and Zeng, An-Ping and Yuan, Jing-Qi: A cybernetic model to describe the dynamics of myeloma cell cultivations. Applied Mathematics and Computation, 205(1): S. 84--97, 2008. , DOI: 10.1016/j.amc.2008.05.066
  • Bommareddy, Rajesh Reddy and Chen, Zhen and Rappert, Sugima and Zeng, An-Ping: A de novo NADPH generation pathway for improving lysine production of Corynebacterium glutamicum by rational design of the coenzyme specificity of glyceraldehyde 3-phosphate dehydrogenase.. Metabolic engineering, 25: S. 30--7, sep 2014. , DOI: 10.1016/j.ymben.2014.06.005, http://www.ncbi.nlm.nih.gov/pubmed/24953302
  • Zhou, Feng and Bi, Jing-Xiu and Zeng, An-Ping and Yuan, Jing-Qi: A macrokinetic and regulator model for myeloma cell culture based on metabolic balance of pathways. Process Biochemistry, 41(10): S. 2207--2217, oct 2006. , DOI: 10.1016/j.procbio.2006.08.001, http://linkinghub.elsevier.com/retrieve/pii/S1359511306003205
  • Kayo, S and Bahnemann, J and Klauser, M and Portner, R and Zeng, A P: A microfluidic device for immuno-affinity-based separation of mitochondria from cell culture. Lab Chip, 13(22): S. 4467-4475, 2013. , DOI: 10.1039/c3lc50739d
  • Ma, C W and Xiu, Z L and Zeng, A P: A new concept to reveal protein dynamics based on energy dissipation. PLoS One, 6(10): S. e26453, 2011. , DOI: 10.1371/journal.pone.0026453
  • Liu, Y H and Bi, J X and Zeng, A P and Yuan, J Q: A population balance model describing the cell cycle dynamics of myeloma cell cultivation. Biotechnol Prog, 23(5): S. 1198--1209, 2007. , DOI: 10.1021/bp070152z
  • Liu, Y H and Bi, J X and Zeng, A P and Yuan, J Q: A simple kinetic model for myeloma cell culture with consideration of lysine limitation. Bioprocess Biosyst Eng, 31(6): S. 569--577, 2008. , DOI: 10.1007/s00449-008-0204-x
  • Stelzer, M and Sun, J and Kamphans, T and Fekete, S P and Zeng, A P: An extended bioreaction database that significantly improves reconstruction and analysis of genome-scale metabolic networks. Integr Biol (Camb), 3(11): S. 1071--1086, 2011. , DOI: 10.1039/c1ib00008j
  • Platas, Oscar B and Jandt, Uwe and Sandig, Volker and Pörtner, Ralf and Zeng, An-Ping: An integrated synchronization approach for studying cell-cycle dependent processes of mammalian cells under physiological conditions. BMC Proceedings, 7(Suppl 6): S. P16, 2013. , DOI: 10.1186/1753-6561-7-S6-P16
  • da Luz, Julian A., Hans, Enrico, Frank, Doinita, Zeng, An-Ping: Analysis of intracellular metabolites of Corynebacterium glutamicum at high cell density with automated sampling and filtration and assessment of engineered enzymes for effective L-lysine production. Engineering in Life Sciences, 17: S. 512-522, 2017. , DOI: 10.1002/elsc.201600163
  • Flipphi, M and Sun, J and Robellet, X and Karaffa, L and Fekete, E and Zeng, A P and Kubiecek, C P: Biodiversity and evolution of primary carbon metabolism in Aspergillus nidulans and other Aspergillus spp. Fungal Genet Biol, 46 Suppl 1: S. S19--S44, 2009.
  • da Silva, M. R. and Hongwu, Ma and An-Ping, Zeng: Centrality, Network Capacity, and Modularity as Parameters to Analyze the Core-Periphery Structure in Metabolic Networks. Proceedings of the IEEE, 96(8): S. 1411--1420, 2008. , DOI: 10.1109/jproc.2008.925418
  • Ma, Hong-Wu and Zeng, An-Ping: Chapter 9 - Reconstruction of Metabolic Networks from Genome Information and Its Structural and Functional Analysis. In Kriete, Andres and Eils, Roland, Hrsg., Computational Systems Biology , S. 169--189. Academic Press, Burlington, 2006. , DOI: 10.1016/B978-012088786-6/50028-9
  • Chen, Z and Meyer, W and Rappert, S and Sun, J and Zeng, A P: Coevolutionary analysis enabled rational deregulation of allosteric enzyme inhibition in Corynebacterium glutamicum for lysine production. Appl Environ Microbiol, 77(13): S. 4352--4360, 2011. , DOI: 10.1128/AEM.02912-10
  • Jandt, U and You, C and Zhang, Y H and Zeng, A P: Compartmentalization and metabolic channeling for multienzymatic biosynthesis: practical strategies and modeling approaches. Adv Biochem Eng Biotechnol, 137: S. 41--65, 2013. , DOI: 10.1007/10\_2013\_221
  • Schomburg, K T and Ardao, I and Gotz, K and Rieckenberg, F and Liese, A and Zeng, A P and Rarey, M: Computational biotechnology: prediction of competitive substrate inhibition of enzymes by buffer compounds with protein-ligand docking. J Biotechnol, 161(4): S. 391--401, 2012. , DOI: 10.1016/j.jbiotec.2012.08.002
  • Chen, Z and Bommareddy, R R and Frank, D and Rappert, S and Zeng, A P: Deregulation of feedback inhibition of phosphoenolpyruvate carboxylase for improved lysine production in Corynebacterium glutamicum. Appl Environ Microbiol, 80(4): S. 1388--1393, 2014. , DOI: 10.1128/AEM.03535-13
  • Ma, C W and Xiu, Z L and Zeng, A P: Discovery of intramolecular signal transduction network based on a new protein dynamics model of energy dissipation. PLoS One, 7(2): S. e31529, 2012. , DOI: 10.1371/journal.pone.0031529
  • Zeng, An-Ping: Editorial: From Biochemical Engineering to Systems Biology. Process Biochemistry, 41(10): S. 2101--2102, oct 2006. , DOI: 10.1016/j.procbio.2006.07.037, http://linkinghub.elsevier.com/retrieve/pii/S1359511306003321
  • Zhou, Li-Bang and Zeng, An-Ping: Engineering a Lysine-ON Riboswitch for Metabolic Control of Lysine Production in Corynebacterium glutamicum. ACS Synthetic Biology, 4(12): S. 1335--1340, dec 2015. , DOI: 10.1021/acssynbio.5b00075, http://pubs.acs.org/doi/10.1021/acssynbio.5b00075
  • Lifu Song and An-Ping Zeng: Engineering cells as robots for parallel and highly sensitive screening of biomolecules under in vivo conditions. Sci. Report, 7(15145), 2017.
  • He, F Q and Wang, W and Zheng, P and Sudhakar, P and Sun, J and Zeng, A P: Essential O2-responsive genes of Pseudomonas aeruginosa and their network revealed by integrating dynamic data from inverted conditions. Integr Biol (Camb), 6(2): S. 215--223, 2014. , DOI: 10.1039/c3ib40180d
  • Ma, C W and Xiu, Z L and Zeng, A P: Exploring signal transduction in heteromultimeric protein based on energy dissipation model. J Biomol Struct Dyn, 2013. , DOI: 10.1080/07391102.2013.855145
  • Geng, F and Chen, Z and Zheng, P and Sun, J and Zeng, A P: Exploring the allosteric mechanism of dihydrodipicolinate synthase by reverse engineering of the allosteric inhibitor binding sites and its application for lysine production. Appl Microbiol Biotechnol, 97(5): S. 1963--1971, 2013. , DOI: 10.1007/s00253-012-4062-8
  • Lei Qin, Lu Liu, An-Ping Zeng, Dong Wei: From low-cost substrates to microbial lipid by oleaginous yeast and microalgae as cell factory. Bioresources Technology, 245: S. 1507-1519, 2017.
  • Zeng, An-Ping: Fundamentals and Application of New Bioproduction Systems. Springer, , 2013
  • Hezaveh S, Zeng A-P, Jandt U: Human Pyruvate Dehydrogenase Complex E2 and E3BP Core Subunits: New Models and Insights from Molecular Dynamics Simulations. Journal of Physical Chemistry B(120): S. 4399–4409, 2016.
  • He, Feng Q and Sauermann, Ulrike and Beer, Christiane and Winkelmann, Silke and Yu, Zheng and Sopper, Sieghart and Zeng, An-Ping and Wirth, Manfred: Identification of molecular sub-networks associated with cell survival in a chronically SIVmac-infected human CD4+ T cell line.. Virology journal, 11(1): S. 152, jan 2014. , DOI: 10.1186/1743-422X-11-152, http://www.virologyj.com/content/11/1/152
  • He, F and Zeng, A P: In search of functional association from time-series microarray data based on the change trend and level of gene expression. BMC Bioinformatics, 7: S. 69, 2006. , DOI: 10.1186/1471-2105-7-69
  • Ardao, I and Hwang, E T and Zeng, A P: In vitro multienzymatic reaction systems for biosynthesis. Adv Biochem Eng Biotechnol, 137: S. 153--184, 2013. , DOI: 10.1007/10\_2013\_232
  • Schopke, B and Zeng, A P: Inference of responsive metabolic pathways from time-series transcriptomic data with consideration of the metabolic network structure. Integr Biol (Camb), 4(8): S. 889--896, 2012. , DOI: 10.1039/c2ib20031g
  • Chen, Z and Rappert, S and Sun, J and Zeng, A P: Integrating molecular dynamics and co-evolutionary analysis for reliable target prediction and deregulation of the allosteric inhibition of aspartokinase for amino acid production. J Biotechnol, 154(4): S. 248--254, 2011. , DOI: 10.1016/j.jbiotec.2011.05.005
  • Rajabi, Negar and Bahnemann, Janina and Tzeng, Tzu-Nen and Platas Barradas, Oscar and Zeng, An-Ping and Müller, Jörg: Lab-on-a-chip for cell perturbation, lysis, and efficient separation of sub-cellular components in a continuous flow mode. Sensors and Actuators A: Physical, 215: S. 136--143, aug 2014. , DOI: 10.1016/j.sna.2013.12.019, http://linkinghub.elsevier.com/retrieve/pii/S0924424713006109
  • Jandt, U and Platas Barradas, O and Portner, R and Zeng, A P: Mammalian cell culture synchronization under physiological conditions and population dynamic simulation. Appl Microbiol Biotechnol, 98(10): S. 4311-4319, 2014. , DOI: 10.1007/s00253-014-5553-6
  • Zhou, Libang; Zeng, An-Ping : Metabolic engineering of Corynebacterium glutamicum for increasing lysine production by using a lysine riboswitch. ACS Synthetic Biology, 2014 (accepted).
  • Bommareddy, Rajesh Reddy and Sabra, Wael and Maheshwari, Garima and Zeng, An-Ping: Metabolic network analysis and experimental study of lipid production in Rhodosporidium toruloides grown on single and mixed substrates. Microbial Cell Factories, 14(1): S. 36, dec 2015. , DOI: 10.1186/s12934-015-0217-5, http://www.microbialcellfactories.com/content/14/1/36
  • Sun, J and Lu, X and Rinas, U and Zeng, A P: Metabolic peculiarities of Aspergillus niger disclosed by comparative metabolic genomics. Genome Biol, 8(9): S. R182, 2007. , DOI: 10.1186/gb-2007-8-9-r182
  • Sabra, W. and Groeger, C. and Zeng, An-Ping: Microbial Cell Factories for Diol Production. In , Hrsg., Advances in Biochemical Engineering/Biotechnology . Springer, 2016. , DOI: 10.1007/10\_2015\_330, http://link.springer.com/10.1007/10\_2015\_330
  • Wurm, M and Schopke, B and Lutz, D and Muller, J and Zeng, A P: Microtechnology meets systems biology: the small molecules of metabolome as next big targets. J Biotechnol, 149(1-2): S. 33--51, 2010. , DOI: 10.1016/j.jbiotec.2010.05.002
  • He, F and Chen, H and Probst-Kepper, M and Geffers, R and Eifes, S and Del Sol, A and Schughart, K and Zeng, A P and Balling, R: PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells. Mol Syst Biol, 8: S. 624, 2012. , DOI: 10.1038/msb.2012.56
  • Ma, C W and Luddecke, J and Forchhammer, K and Zeng, A P: Population shift of binding pocket size and dynamic correlation analysis shed new light on the anticooperative mechanism of PII protein. Proteins, 82(6): S. 1048--1059, 2014. , DOI: 10.1002/prot.24477
  • H. Zhao, A.-P. Zeng: Preface: Exploring the Synergy between Synthetic Biology and Metabolic Engineering , , Jg. 162 of Synthetic Biology - Metabolic Engineering, S. V-Vi. Springer, , 2017.
  • José-Aníbal Mora-Villalobos and An-Ping Zeng: Protein and pathway engineering for the biosynthesis of 5-hydroxytryptophan in Escherichia coli. Eng. Life Sci, 17: S. 892-899, 2017.
  • Chen, Zhen and Geng, Feng and Zeng, An-Ping: Protein design and engineering of a de novo pathway for microbial production of 1,3-propanediol from glucose. Biotechnology Journal, 10(2): S. 284--289, feb 2015. , DOI: 10.1002/biot.201400235, http://doi.wiley.com/10.1002/biot.201400235
  • Chen, Z and Zeng, A P: Protein design in systems metabolic engineering for industrial strain development. Biotechnol J, 8(5): S. 523--533, 2013. , DOI: 10.1002/biot.201200238
  • Chen Z, Zeng A-P: Protein engineering approaches to chemical biotechnology. Curr Opin Biotechnol(42): S. 198–205, 2016.
  • Chen L, Zeng A-P: Rational Design and Metabolic Analysis of Escherichia coli for Effective Production of L-Tryptophan at High Concentration. Appl Microbiol Biotechnol , 15(101): S. 559-568, 2017. , DOI: doi: 10.1007/s00253-016-7772-5
  • Chen, Z and Rappert, S and Zeng, A P: Rational Design of Allosteric Regulation of Homoserine Dehydrogenase by a Non-Natural Inhibitor L-Lysine. ACS Synth Biol, 2013. , DOI: 10.1021/sb400133g
  • Chen, Zhen and Rappert, Sugima and Zeng, An-Ping: Rational Design of Allosteric Regulation of Homoserine Dehydrogenase by a Nonnatural Inhibitor L-Lysine. ACS Synthetic Biology, 4(2): S. 126--131, feb 2015. , DOI: 10.1021/sb400133g, http://pubs.acs.org/doi/abs/10.1021/sb400133g
  • Jin Guo, Samira Hezaveh, Jana Tatur, An-Ping Zeng, Uwe Jandt: Reengineering of human pyruvate dehydrogenase complex: from disintegration to highly active agglomerates. Biochemical Journal, 474(5): S. 865-875, 2017. , DOI: 10.1042/BCJ20160916
  • Feng Geng, Cheng-Wei Ma and An-Ping Zeng : Reengineering substrate specificity of E. coli glutamate dehydrogenase using a position-based prediction method. . Biotechnol. Letter , 39(4), 2017.
  • He, F and Balling, R and Zeng, A P: Reverse engineering and verification of gene networks: principles, assumptions, and limitations of present methods and future perspectives. J Biotechnol, 144(3): S. 190--203, 2009. , DOI: 10.1016/j.jbiotec.2009.07.013
  • Jandt, U and Shao, S and Wirth, M and Zeng, A P: Spatiotemporal modeling and analysis of transient gene delivery. Biotechnol Bioeng, 108(9): S. 2205--2217, 2011. , DOI: 10.1002/bit.23175
  • Chen, Z and Wilmanns, M and Zeng, A P: Structural synthetic biotechnology: from molecular structure to predictable design for industrial strain development. Trends Biotechnol, 28(10): S. 534--542, 2010. , DOI: 10.1016/j.tibtech.2010.07.004
  • Chen, L and Chen, Z and Zheng, P and Sun, J and Zeng, A P: Study and reengineering of the binding sites and allosteric regulation of biosynthetic threonine deaminase by isoleucine and valine in Escherichia coli. Appl Microbiol Biotechnol, 97(7): S. 2939--2949, 2013. , DOI: 10.1007/s00253-012-4176-z
  • Barradas, Oscar Platas and Jandt, Uwe and Becker, Max and Bahnemann, Janina and Pörtner, Ralf and Zeng, An-Ping: Synchronized mammalian cell culture: Part I-A physical strategy for synchronized cultivation under physiological conditions. Biotechnology Progress, 31(1): S. 165--174, jan 2015. , DOI: 10.1002/btpr.1944, http://doi.wiley.com/10.1002/btpr.1944
  • Jandt, Uwe and Platas Barradas, Oscar and Pörtner, Ralf and Zeng, An-Ping: Synchronized mammalian cell culture: Part II-population ensemble modeling and analysis for development of reproducible processes. Biotechnology Progress, 31(1): S. 175--185, jan 2015. , DOI: 10.1002/btpr.2006, http://doi.wiley.com/10.1002/btpr.2006
  • Cheng-Wei Ma, Li-Bang Zhou and An-Ping Zeng: Synthetic Biology and Metabolic Engineering. Adv. Biochem. Eng. /Biotechnol., Kapitel Engineering Biomolecular Switches for Dynamic Metabolic Control, S. 45-76. Springer, , 2017, DOI: 10.1007/10_2016_9.
  • H. Zhao, and A.-P. Zeng: Synthetic Biology–Metabolic Engineering, Jg. 162. Springer, , 2017
  • José-Aníbal Mora-Villalobos and An-Ping Zeng: Synthetic pathways and processes for effective production of 5-hydroxytryptophan and serotonin from glucose in Escherichia coli. J. Biol. Eng. (Accepted), 2017.