前天，不是昨天，我做了一个奇怪的梦，今天才决定把它写进博文里。 80-90年代，基于对时空、物质、能量与信息，宇宙与生命的思考，我认为结构是比时空更根本的概念；因此，86年写作《结构论》时采用英文“Structurity”对于相对论（relativity）的词汇后缀。 90年代-21世纪初在海外的十载，每次面试时，总有教授问及我简历中的“Structurity”和“Pan-Evolution Theory”，当我提及基于以上原因和达尔文进化论基础上提出生物系统（Biosystems）的进化理论时，有些说到在中国那样的环境不可能产生爱恩斯坦那样的理论。 问题是，我并不是要或认为自己要与世界最伟大的科学理论家去比拟，而只是借鉴了一个术语的表达或造词汇的方式而已。 前天，夜里的一个梦是爱恩斯坦老态龙钟，手里拿着一本发黄的中译本相对论，里面还有几页撕裂了，还我跟他在一个山坡上躺着和坐着，他在书中夹带绵袄类的布料或是布料与书夹杂一起，他走开在旁边，还我就在仔细地阅读和思考那书中的数学方程式和演算方法。 醒来后，确实觉得奇怪，不知道是何意？今天才决定写下来，以免忘记了。 - “相对论与结构论”（ http://blog.sina.com.cn/s/blog_825f70010100sz84.html ） - ：“结构论 - 生物系统的泛进化理论”英文介绍1999年我建立网站在线刊登，主要是分子、细胞到器官、个体系统的节律稳态模型和系统论、生物技术和生物信息技术，生物系统和人工生物系统的系统生物科学与工程等观点。 当时，为许多著名研究机构的生物信息学网页链接，比如，以色列魏兹曼研究所，北京医科大学等，另，惊奇的还有国际上一物理学家将其链接在弦论的网页上等。 （我的生物系统模型图 - 1999年在线） （我的节律稳态原理图 - 1999年在线） （2007年Alon的系统生物学著作 - 封面图，另，Nature上有科学家发表系统生物学与合成生物学的“Oscillator”、“structure theory”等理论论文） （我1999年筹办国际会议的细胞分子电子学与转基因整合 - 原理图，会议通知和网站地址1999年刊登在 Nature和Kybernetes等 ） ：90年代我的国内文章的英译：On the concept of system biological engineering, Transgenic animal expression system - transgenic egg plan (Goldegg Plan), Transgenic avian used as oviduct bioreactor for pharmaceutical expression, From positive to synthetic medical science, Structure theory of self-organization systems, Communication on Transgenic Animals, 1994- 1996. （图片版权所有，未经许可不得转载）
Provider: Quertle (www.quertle.info) Content: text/plain; charset=UTF-8 TY- JOUR TI- How molecular should your molecular model be? On the level of molecular detail required to simulate biological networks in systems and synthetic biology. AU- Gonze, Didier AU- Abou-Jaoud, Wassim AU- Ouattara, Djomangan Adama AU- Halloy, Jos PY- 2011 T2- Methods in enzymology J2- Methods Enzymol UR- http://www.ncbi.nlm.nih.gov/pubmed/21187226 VL- 487 SP- 171-215 N2- The recent advance of genetic studies and the rapid accumulation of molecular data, together with the increasing performance of computers, led researchers to design more and more detailed mathematical models of biological systems. Many modeling approaches rely on ordinary differential equations (ODE) which are based on standard enzyme kinetics. Michaelis-Menten and Hill functions are indeed commonly used in dynamical models in systems and synthetic biology because they provide the necessary nonlinearity to make the dynamics nontrivial (i.e., limit-cycle oscillations or multistability). For most of the systems modeled, the actual molecular mechanism is unknown, and the enzyme equations should be regarded as phenomenological. In this chapter, we discuss the validity and accuracy of these approximations. In particular, we focus on the validity of the Michaelis-Menten function for open systems and on the use of Hill kinetics to describe transcription rates of regulated genes. Our discussion is illustrated by numerical simulations of prototype systems, including the Repressilator (a genetic oscillator) and the Toggle Switch model (a bistable system). We systematically compare the results obtained with the compact version (based on Michaelis-Menten and Hill functions) with its corresponding developed versions (based on elementary reaction steps and mass action laws). We also discuss the use of compact approaches to perform stochastic simulations (Gillespie algorithm). On the basis of these results, we argue that using compact models is suitable to model qualitatively biological systems. N1- Exported from www.Quertle.info. Search query: Synthetic biology. ER- TY- JOUR TI- Large-Scale Discovery and Characterization of Protein Regulatory Motifs in Eukaryotes AU- Lieber, Daniel S AU- Elemento, Olivier AU- Tavazoie, Saeed PY- 2010 T2- PLoS ONE J2- PLoS One UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012054/ VL- 5 IS- 12 DO- 10.1371/journal.pone.0014444 C2- 3012054 N2- The increasing ability to generate large-scale, quantitative proteomic data has brought with it the challenge of analyzing such data to discover the sequence elements that underlie systems-level protein behavior. Here we show that short, linear protein motifs can be efficiently recovered from proteome-scale datasets such as sub-cellular localization, molecular function, half-life, and protein abundance data using an information theoretic approach. Using this approach, we have identified many known protein motifs, such as phosphorylation sites and localization signals, and discovered a large number of candidate elements. We estimate that 80% of these are novel predictions in that they do not match a known motif in both sequence and biological context, suggesting that post-translational regulation of protein behavior is still largely unexplored. These predicted motifs, many of which display preferential association with specific biological pathways and non-random positioning in the linear protein sequence, provide focused hypotheses for experimental validation. N1- Exported from www.Quertle.info. Search query: Synthetic biology. ER- TY- JOUR TI- Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms. AU- Medema, Marnix H AU- Breitling, Rainer AU- Bovenberg, Roel AU- Takano, Eriko PY- 2010 T2- Nature reviews. Microbiology J2- Nat Rev Microbiol UR- http://www.ncbi.nlm.nih.gov/pubmed/21189477 N2- One of the most promising applications of synthetic biology is the biosynthesis of new drugs from secondary metabolites. Here, we survey a wide range of strategies that control the activity of biosynthetic modules in the cell in space and time, and illustrate how these strategies can be used to design efficient cellular synthetic production systems. Re-engineered versions of secondary metabolite biosynthetic pathways identified from any genomic sequence can then be inserted into these systems in a plug-and-play fashion. N1- Exported from www.Quertle.info. Search query: Synthetic biology. ER- TY- JOUR TI- Introduction of customized inserts for streamlined assembly and optimization of BioBrick synthetic genetic circuits. AU- Norville, Julie E AU- Derda, Ratmir AU- Gupta, Saurabh AU- Drinkwater, Kelly A AU- Belcher, Angela M AU- Leschziner, Andres E AU- Knight, Thomas F, Jr PY- 2010 T2- Journal of biological engineering J2- J Biol Eng UR- http://www.ncbi.nlm.nih.gov/pubmed/21172029 VL- 4 IS- 1 SP- 17 N2- ABSTRACT: BACKGROUND: BioBrick standard biological parts are designed to make biological systems easier to engineer (e.g. assemble, manipulate and modify). There are over 5,000 parts available in the Registry of Standard Biological Parts that can be easily assembled into genetic circuits using a standard assembly technique. The standardization of the assembly technique has allowed for wide distribution to a large number of users -- the parts are reusable and interchangeable during the assembly process. The standard assembly process, however, has some limitations. In particular it does not allow for modification of already assembled biological circuits, addition of protein tags to pre-existing BioBrick parts, or addition of non-BioBrick parts to assemblies. RESULTS: In this paper we describe a simple technique for rapid generation of synthetic biological circuits using introduction of customized inserts. We demonstrate its use in Escherichia coli (E. coli) to express green fluorescent protein (GFP) at pre-calculated relative levels and to add an N-terminal tag to GFP. The technique uses a new BioBrick part (called a BioScaffold) that can be inserted into cloning vectors and excised from them to leave a gap into which other DNA elements can be placed. The removal of the BioScaffold is performed by a Type IIB restriction enzyme (REase) that recognizes the BioScaffold but cuts into the surrounding sequences; therefore, the placement and removal of the BioScaffold allows the creation of seamless connections between arbitrary DNA sequences in cloning vectors. The BioScaffold contains a built-in red fluorescent protein (RFP) reporter; successful insertion of the BioScaffold is, thus, accompanied by gain of red fluorescence and its removal is manifested by disappearance of the red fluorescence. CONCLUSIONS: The ability to perform targeted modifications of existing BioBrick circuits with BioScaffolds (1) simplifies and speeds up the iterative design-build-test process through direct reuse of existing circuits, (2) allows incorporation of sequences incompatible with BioBrick assembly into BioBrick circuits (3) removes scar sequences between standard biological parts, and (4) provides a route to adapt synthetic biology innovations to BioBrick assembly through the creation of new parts rather than new assembly standards or parts collections. N1- Exported from www.Quertle.info. Search query: Synthetic biology. ER- TY- JOUR TI- Cellulase-Xylanase Synergy in Designer Cellulosomes for Enhanced Degradation of a Complex Cellulosic Substrate AU- Moras, Sarah AU- Barak, Yoav AU- Caspi, Jonathan AU- Hadar, Yitzhak AU- Lamed, Raphael AU- Shoham, Yuval AU- Wilson, David B AU- Bayer, Edward A PY- 2010 T2- mBio J2- mBio UR- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999897/ VL- 1 IS- 5 DO- 10.1128/mBio.00285-10 C2- 2999897 N2- IMPORTANCE: Global efforts towards alternative energy programs are highlighted by processes for converting plant-derived carbohydrates to biofuels. The major barrier in such processes is the inherent recalcitrance to enzymatic degradation of cellulose combined with related associated polysaccharides. The multienzyme cellulosome complexes, produced by anaerobic bacteria, are considered to be the most efficient systems for degradation of plant cell wall biomass. In the present work, we have employed a synthetic biology approach by producing artificial designer cellulosomes of predefined enzyme composition and architecture. The engineered tetravalent cellulosome complexes contain two different types of cellulases and two distinct xylanases. Using this approach, enhanced synergistic activity was observed on wheat straw, a natural recalcitrant substrate. The present work strives to gain insight into the combined action of cellulosomal enzyme components towards the development of advanced systems for improved degradation of cellulosic material. N1- Exported from www.Quertle.info. Search query: Synthetic biology. ER-
《自然》杂志预测2011年科研热点 http://news.sciencenet.cn//htmlnews/2011/1/242378.shtm 合成生物学：想想多细胞 科学家不用非得通过单个细胞弄清复杂的合成生物学了，我们可以期待有更多关于细胞群体行为的文章在今年发表。利用细菌来制药或许会成为现实。 New year, new science http://www.nature.com/news/2010/101231/full/469012a.html Synthetic biology: think multicellular No longer will scientists have to cram complicated synthetic biology into a single cell. Last year, researchers engineered an entire colony of bacteria to periodically fluoresce in unison, and we can expect many more papers exploring the behaviour of collections of cells. The goal is to exploit this teamwork to give bacteria useful functions such as producing medicinal drugs. http://www.gopubmed.org/web/gopubmed/1?WEB01lys5moqoa0ueI1tI37I00h001000j100200010 142 documents semantically analyzed 1 2 Top Years Publications 2007 17 2009 14 2004 12 2008 11 2005 9 2010 8 2006 8 1999 7 1988 7 2003 6 2001 6 2000 5 2002 5 1998 5 1997 3 1996 3 1995 2 1994 2 1992 2 1984 2 1 2 1 2 Top Countries Publications USA 55 Germany 11 Japan 9 Switzerland 7 Canada 6 China 5 Australia 5 United Kingdom 5 Spain 4 South Korea 4 Netherlands 3 Poland 2 Czech Republic 2 France 2 Hungary 2 Italy 2 Norway 2 Austria 1 Romania 1 Denmark 1 1 2 1 2 3 4 5 Top Cities Publications Mainz 4 San Diego 4 Princeton 4 Seoul, South Korea 4 Columbia, MO, USA 3 Basel 3 Bethesda 3 Austin 3 Chicago 3 Barcelona 2 Prague 2 Berkeley 2 Durham 2 Mnster 2 Madison 2 Budapest, Hungary 2 East Lansing 2 Pasadena, CA, USA 2 Salt Lake City 2 Guangzhou 2 1 2 3 4 5 1 2 3 ... 6 Top Journals Publications P Natl Acad Sci Usa 8 Nature 4 Biomaterials 4 J Bacteriol 3 Tissue Eng 3 J Biol Chem 3 J Cell Physiol 3 Curr Opin Biotechnol 2 J Am Chem Soc 2 Birth Defects Res C Embryo Today 2 Tissue Eng Part A 2 In Vitro Cell Dev-an 2 Cancer Res 2 J Cell Sci 2 J Appl Genet 1 Physiol Res 1 Bmc Syst Biol 1 Febs J 1 Arthritis Rheum 1 J Theor Biol 1 1 2 3 ... 6 1 2 3 ... 115 Top Terms Publications Animals 80 Humans 53 Proteins 42 Genes 42 extracellular region 31 Tissues 31 Peptides 27 Nature 25 Extracellular Matrix 24 Mice 24 Cells, Cultured 24 signal transduction 22 extracellular matrix 21 Models, Biological 20 Membranes 19 membrane 19 Amino Acid Sequence 19 Cell Adhesion 19 Biology 18 Gene Expression 18 1 2 3 ... 115 1 2 3 ... 28 Top Authors Publications Mller W 3 Cho C 3 Seo S 3 Akaike T 3 Quinn T 3 Glinsky V 3 Glinsky G 3 Weber W 2 Schroeder H 2 Wiens M 2 Hubbell J 2 Zhou T 2 Basu S 2 Choi Y 2 Mossine V 2 Deutscher S 2 Nie Q 2 Lee D 1 Kiener H 1 Watts G 1 1 2 3 ... 28
http://news.sciencenet.cn/htmlnews/2010/10/238594.shtm 美人造生命小组发明迄今最简单有效基因合成技术 http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi National Library of Medicine - Medical Subject Headings 2011 MeSH MeSH Descriptor Data Return to Entry Page Standard View. Go to Concept View ; Go to Expanded Concept View MeSH Heading Synthetic Biology 合成生物学 Tree Number H01.158.273.904 Tree Number J01.293.069.500 Annotation IM for the discipline (education, history, etc); NIM as a coordinate for studies involving specific synthetic biology concepts and applications Scope Note A field of biological research combining engineering in the formulation, design, and building (synthesis) of novel biological structures, functions, and systems. Allowable Qualifiers CL EC ED ES HI IS LJ MA MT OG SN ST TD History Note 2011 Date of Entry 20100625 Unique ID D058615 MeSH Tree Structures Natural Science Disciplines Biological Science Disciplines Biology Botany + Computational Biology + Cell Biology Developmental Biology + Ecology + Exobiology Genetics + Laboratory Animal Science Microbiology + Natural History Neurobiology Parasitology + Photobiology Radiobiology Sociobiology Synthetic Biology Zoology + Technology, Industry, and Agriculture Engineering Bioengineering Synthetic Biology http://www.gopubmed.org/web/gopubmed/1?WEB0k2h0lw1ovzpeI8IdI0 13,100 documents semantically analyze 1 2 3 Top Years Publications 2009 912 2010 840 2007 776 2008 775 2006 650 2005 618 2004 542 2002 530 2003 512 2000 506 1998 481 2001 475 1999 468 1997 446 1996 442 1993 439 1995 431 1992 428 1994 427 1990 409 1 2 3 1 2 3 4 5 Top Countries Publications USA 6,095 United Kingdom 767 Japan 570 Germany 556 Canada 417 China 359 Italy 313 India 252 Australia 234 Sweden 233 Spain 207 Netherlands 191 France 181 Russia 155 Switzerland 140 Denmark 107 South Korea 99 Israel 96 Belgium 91 Brazil 66 1 2 3 4 5 1 2 3 ... 48 Top Cities Publications Los Angeles 408 Bethesda 348 Cambridge, USA 337 Houston 250 New York City 240 Boston 239 Berkeley 182 Philadelphia 154 London 152 Tokyo 134 St. Louis 131 Baltimore 129 Chicago 116 Moscow, Russia 112 Cambridge 102 San Diego 100 Edinburgh 98 Stockholm, Sweden 97 Austin 89 Heidelberg 88 1 2 3 ... 48 1 2 3 ... 110 Top Journals Publications J Biol Chem 714 P Natl Acad Sci Usa 357 Biochemistry-us 250 Nucleic Acids Res 219 J Am Chem Soc 180 Contraception 137 Biochim Biophys Acta 135 Biochem Bioph Res Co 125 Febs Lett 117 J Mol Biol 114 Mol Cell Biol 112 Vaccine 110 J Virol 103 J Immunol 100 J Cell Biol 95 Science 94 Genetics 91 Cancer Res 79 Nature 77 Biochem J 76 1 2 3 ... 110 1 2 3 ... 1600 Top Terms Publications Animals 6,064 Humans 5,147 Proteins 5,091 Peptides 3,574 Genes 3,075 Amino Acid Sequence 2,645 Biology 2,024 DNA 1,950 Mice 1,920 Nature 1,878 Base Sequence 1,675 Amino Acids 1,499 Antibodies 1,475 antigen binding 1,467 Enzymes 1,445 Membranes 1,244 membrane 1,243 Mutation 1,206 Rats 1,195 Binding Sites 1,180 1 2 3 ... 1600 1 2 3 ... 2158 Top Authors Publications Kleinman H 55 Yamada Y 35 Nicolaou K 34 Baird D 34 Nagaraj R 28 Firestone G 28 Fidler I 27 Schreiber S 25 Nomizu M 25 Thyberg J 25 Holm R 24 Schlom J 24 Rivier J 24 Takemoto L 24 Janda K 22 Rebek J 21 Corey E 21 Gait M 20 Reichert L 19 Bygdeman M 19 1 2 3 ... 2158
众所周知，紫杉醇是重要的抗癌药物，其作用机制是抑制癌细胞的有丝分裂。紫杉醇对包括乳腺癌在内的多种癌症有很好的治疗效果，其最高销售额曾超过10亿美元。虽然随着专利的到期，其售价有了较大幅度的降低，但是其价格仍然相当昂贵，一个疗程的价格超过1万美元。 紫杉醇是植物来源的抗癌药物，最初治疗一个病人需要4-5棵太平洋红豆杉的树皮。由于太平洋红豆杉数量非常有限，生长周期很长，并且剥去红豆杉树皮后回导致红豆杉的死亡，因此使用红豆杉树皮来提取紫杉醇治疗癌症病人面临很强的伦理困境。面对此两难境地，科学家发挥科学创新精神，开发出了红豆杉植物细胞培养技术来获取紫杉醇，随着研究是深入，科学家发现可将使用decorative yew的树叶提取紫杉醇的前体，使用化学合成的方法合成紫杉醇。由于decorative yew树叶来源很广，使用树叶也不会杀死树木本身，加之后续合成的高效性，这种提取加合成的方法称为紫杉醇的主要来源。化学全合成是获得化合物的主要手段之一，科学家经过努力也成功地合成了紫杉醇，由于紫杉醇结构复杂，化学合成需要35-50步，得率很低，因此紫杉醇的化学全合成科学意义很大，实际应用的价值不大。 微生物具有底物利用广泛，生长速度快，研究深入，大规模生产容易等优点，非常适合药物的生产，与紫杉醇同为萜类化合物的青蒿素已经通过精确的途径改造和优化，已经实现了工业化生产，这表明通过代谢工程和合成生物学手段在微生物中合成宿主本身不产生的复杂小分子是可行的，也为后续的相关研究提供可供借鉴的策略和经验。 美国麻省理工大学和Tufts大学科学家沿着这个思路，合成紫杉醇的前体taxadiene和 taxadiene-5-alpha-ol。虽然大肠杆菌并不能够产生这两种物质，但是合成他们的前体IPP是大肠杆菌生理代谢过程中的一个中间产物，IPP能够通过两部的酶促反应合成taxadiene。催化后续两部反应的酶类已经从植物中克隆出来。美国科学家首先优化了IPP的生物合成，以大量生成IPP为后续的酶促反应提供底物。 IPP的生物合成有8个步骤，研究发现其中的四个步骤是限速步骤，通过提高限速步骤的酶量，控制整个催化的效率，大量的合成了IPP。接着讲植物的催化酶引入到工程菌株中，优化催化酶的密码子和表达水平，产生了大量的taxadiene。与只加入催化酶没有进行相关优化相比，其产量提高了1500倍，也比已有的文献报道的产量提高了1000倍。接着科学家有加入能够催化taxadiene合成 taxadiene-5-alpha-ol的酶类，将合成紫杉醇的途径有往前迈了一步。虽然离合成能够化学转化的前体浆果赤霉素（baccatin III）还有比较远的距离，但是本研究表明在弄清楚紫杉醇的合成途径后，使用大肠杆菌合成紫杉醇很有潜力。 本研究中使用的平台技术和手段对合成其他化合物具有通用性，因此使用代谢工程结合合成生物学手段将开启动植物来源的活性小分子微生物表达的大门。 Source: “Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli” by Parayil Kumaran Ajikumar, Wen-Hai Xiao, Keith E. J. Tyo, Yong Wang, Fritz Simeon, Effendi Leonard, Oliver Mucha, Too Heng Phon, Blaine Pfeifer, Gregory Stephanopoulos. Science, 1 October, 2010. Funding: Singapore-MIT Alliance, National Institutes of Health and a Milheim Foundation Grant for Cancer Research
标签: 合成生物学
