Systems Metabolic Engineering Design Fatty Acid Production as an Emerging Case Study
多元模块工程在代谢工程中的应用与研究进展
2016年第35卷第11期 CHEMICAL INDUSTRY AND ENGINEERING PROGRESS·3619·化 工 进 展多元模块工程在代谢工程中的应用与研究进展刘丁玉1，2，3，孟娇1，2，3，王智文1，2，3，陈涛1，2，3，赵学明1，2，3（1天津大学化工学院，天津 300072；2教育部系统生物工程重点实验室，天津 300072；3天津化学化工协同创新中心，天津 300072）摘要：随着代谢工程理论体系的发展，代谢工程的研究方法目前已从对单一途径的调控转变为对整个代谢网络的全局调控。
同时，为了在工业微生物领域实现与化学工业生产规模相当的生物炼制过程，代谢工程需要一套通用的菌株优化策略。
其中关键问题之一，是解决代谢通量的不平衡。
本文介绍了基于传统的理性代谢工程与近年来兴起的组合工程中存在的问题，研究者提出了一种模块化的代谢网络优化策略——多元模块工程（multivariate modular metabolic engineering ，MMME ）。
阐述了多元模块工程的原理和方法，列举了其常用的调控技术和手段，在此基础上综述了近年来模块化策略在代谢工程领域的应用进展，提出了该策略面临的主要问题并展望了其未来的发展方向。
关键词：多元模块工程；代谢工程；组合工程；合成生物学中图分类号：Q819 文献标志码：A 文章编号：1000–6613（2016）11–3619–08 DOI ：10.16085/j.issn.1000-6613.2016.11.035Progress and application on multivariate modular metabolic engineeringin metabolic engineeringLIU Dingyu 1，2，3，MENG Jiao 1，2，3，WANG Zhiwen 1，2，3，CHEN Tao 1，2，3，ZHAO Xueming 1，2，3（1School of Chemical Engineering and Technology ，Tianjin University ，Tianjin 300072，China ；2Key Laboratory of Systems Bioengineering ，Ministry of Education ，Tianjin 300072，China ；3Collaborative Innovation Center of ChemicalScience and Engineering ，Tianjin 300072，China ）Abstract ：With the development of metabolic engineering ，the metabolic engineering research method of single pathway regulation has evolved into global metabolic network regulation. In order to realize the chemical industrial vision of ‘biorefineries’ in the field of industrial biotechnology ，metabolic engineering requires a systematic study with well-defined principles and tools. One of the key problems is balancing metabolic flux. Based on the traditional ，rational metabolic engineering and the rise of the problems existing in the combinatorial engineering in recent years ，the researchers proposed a modular metabolic network optimization strategy using multiple module projects. The modular strategies in progress of application in metabolic engineering during recent years are summarized. In addition ，the main problem and future direction of this strategy to optimize metabolic pathways are presented in light of the current knowledge of multiple module application.Key words ：multivariate modular metabolic engineering ；metabolic engineering ；combinatorial engineering ；synthetic biology第一作者：刘丁玉（1987—），男，博士研究生，E-mail*****************.cn ；孟娇（1990—），女，硕士研究生，E-mail ****************.cn 。
代谢工程概述-PPT
（1）基因工程技术的应用 （2）常规诱变技术的应用
2、 生物合成途径的代谢调控
（1）生物合成中间产物的定量生物测定 （2）共合成法在生物合成中的应用 （3）酶的诱导合成和分解代谢产物阻遏
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3、研究生物合成机制的常用方法
（1）刺激实验法 （2）同位素示踪法 （3）洗涤菌丝悬浮法 （4）无细胞抽提法 （5）遗传特性诱变法
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• 1. 生物能支撑观点 • 微生物细胞是工业发酵产物的生产者，微生物细胞的
生长和维持需要由其自身的能量转换机构或从其他形 式的能量转化形成的生物能来支撑。因此，工业发酵 具有生物学属性。
• 2. 代谢网络观点 • 由生化反应网络和跨输送步骤组成的代谢网络既没有
绝对的起点，也没有绝对的终点。代谢网络中任何一 种中间产物(或可借助生物学、化学方法与代谢网络联 网的任何一种化合物)都可能被开发成为工业发酵的目 的产物或原料。
简而言之，代谢工程是生物化学反应代谢网络有目的 的修饰。
代谢工程要解决的主要问题就是改变某些途径中的碳 架物质流量或改变碳架物质流在不同途径中的流量分布。 其目标就是修饰初级代谢，将碳架物质流导入目的产物 的载流途径以获得产物的最大转化率。
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代谢工程的主要特征就是利用DNA重组技术， 重建代谢网络，改变代谢流及分支代谢速度， 以改进代谢产物及蛋白类产品，由于外源 DNA的引入扩展了固有的代谢途径，获得了 新的化学物质。改变转化蛋白的过程，减少 不必要的废物。例如，谷氨酸发酵
“中心途径”和“离心途径”等连续的代谢途径的代谢，才能在胞内生成目的
产物，最后，目的产物跨过细胞质膜排出细胞回到培养介质中。
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1、胞外酶对原料的降解及营养物质进入细 胞的过程 2、经胞内降解代谢途径汇入中心代谢途径 3、中心代谢途径及其控制 4、合成代谢流及其控制 5、目的产物的跨膜及其控制
代谢工程概述
代谢工程的一些基本定义
代谢流和碳骨架物质流：代谢物在代谢途径中 流动形成代谢流。在代谢工程领域代谢流往往 是指骨架物质流。
代谢主流：在一定的培养条件下，代谢物再代 谢网络中流动，流量相对集中的代谢流叫做该 条件下的代谢主流。代谢途径的延伸和改变都 会改变代谢主流，从而实现新基质的利用和新 产品的开发。代谢主流的测定是代谢工程的重 要组成部分。
代谢工程的一些基本定义
载流途经：代谢主流流经的代谢途径为主要载流途经， 简称载流途经。在代谢工程研究中载流途经是指碳流 在代谢网络中通过的主要途径。
代谢主流的变动性和选择性：生物细胞的代谢主流处 于不断的变化之中，其方向、流量甚至代谢主流的载 流途经都可能发生变化。这就是代谢主流的变动性和 代谢主流对代谢网络途径的选择性。这种变动和选择 的根据在于生物细胞的遗传物质，选择的原因在于细 胞所处的环境条件的变化。
（2）共合成法在生物合成中的应用
（3）酶的诱导合成和分解代谢产物阻遏
（4）无机磷对生物合成的调节
3.研究生物合成机制的常用方法
（1）刺激实验法
（2）同位素示踪法
（3）洗涤菌丝悬浮法
（4）无细胞抽提法
（5）遗传特性诱变法
代谢工程的研究方法
1分子生物学方法：构建特殊的基因转移系统，尤其对于具有较 高生产价值的微生物，具有重要意义。例如Backman等利用切 割载体获得Tyr营养突变型，为构建苯丙氨酸的生产菌株奠定基 础。
途径工程，张惠展，2003 基因工程原理，吴乃虎，2004 代谢工程，张蓓等，天津大学出版社，2003
01绪论 代谢工程概述 授课教师：李强
本章内容
§1.1代谢工程的产生和概念的演变 §1.2代谢工程的研究内容 §1.3 代谢工程的应用领域和前景
Systems Engineering Management
Interfaces
– In larger projects, interfaces between groups/subsystems must be well-defined. – Two types of interfaces: physical and functional. – Interface violations will happen. Need to be arbitrated at next highest level. – Keep your interfaces to the outside world simple, clear, defined, and consistent.
ห้องสมุดไป่ตู้
Definitions
What is Systems Engineering?
– the ensemble of coordinated analyses, simulations, and processes which lead to a technical product which best meets the needs of an identified customer.
Systems Engineering Management
FLEX
1.0 MANAGEMENT 1.1 Project Planning & Schedule 1.1.1 Organization and Meetings 1.1.2 Schedule Maintenance 1.1.3 Implem & Work-around Plans 1.2 Financial 1.2.1 Budget Update & Forecast 1.2.2 Subcontract Monitoring 1.3 Task Manage & Tracking 1.3.1 Monitoring & Tracking 1.3.2 WBS Maintenance 1.4 Interface 1.4.1 Program Monitor 1.4.2 JSC RMS Program 1.4.3 Tech. Tracking Committee 1.4.4 Reporting 1.5 Co-I & Subcontractor Mgmt 1.5.1 Planning & Schedule 1.5.2 Technical & Task Tracking 1.6 Quality 1.6.1 Quality Program Plan 1.6.2 Nonconformance Tracking 2.0 SYSTEM ENGINEERING 2.1 Requirements 2.1.1 Expt Req Document 2.1.2 Subsystem Req. Documents 2.2 Design & Evaluation 2.2.1 3-D 1-g & 0-g Modeling 2.2.2 Feedforward Control Design 2.2.3 Feedback Control Design 2.2.4 Human-in-the-Loop Simulation 2.2.5 Performance Evaluation 2.3 Configuration Control 2.3.1 Design Documents 2.3.2 Processing &Tracking 2.3.3 Equipment List Maintenance 2.3.4 Test Matrix 2.4 Program Reviews 2.4.1 Conceptual Design Review 2.4.2 Requirements Review 2.4.3 Non-Advocate Review 2.4.4 Preliminary Design Review 2.4.5 Critical Design Review 2.4.6 Flight Readiness Review 2.4.7 Post Mission Expt Review 3.0 HARDWARE DESIGN & FAB 3.1 Arm Fabrication 3.1.1 Prototype (1) 3.1.2 Ground Test Facilities (2) 3.1.3 Flight Arms (2) 3.1.4 Motors 3.1.5 Payloads 3.3 Human Interface 3.3.1 Joystick 3.3.2 Grid W/S/W 3.3.3 Task Targets 3.3.4 Video Interface 3.2 Support Elec & Software 3.2.1 Experiment Support Module 3.2.2 Crew Interface 3.2.3 Ground Support Equipment 3.2.4 Software 3.2.5 Up/downlink Refurbishment
SystemEngineering
Lesson One Fundamentals of Systems
2. role and responsibility of the systems engineer
• The systems engineer wg the development of the system architecture, defining and allocating requirements, evaluating design tradeoffs, balancing technical risk between systems, defining and assessing interfaces, providing oversight of verification and validation activities, as well as many other tasks.
System_Engineering
contents
• Fundamentals of Systems Engineering • Program/Project Life Cycle • System Design • Product Realization • Crosscutting Technical Management
• The systems engineer reviews and evaluates the technical aspects of the project to ensure that the systems/subsystems engineering processes are functioning properly and evolves the system from concept to product. The entire technical team is involved in the systems engineering process.
代谢工程概述
• 随后，核酸类物质发酵产生菌也以代谢控制发酵
理论为指导进行选育，并奋起直追成为后起之秀。
实用文档
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• 氨基酸和核苷酸发酵的研究进一步推动了抗生素 发酵的研究与生产，发酵由野生型发酵向高度人 为控制的发酵转移；由依赖于微生物分解代谢的 发酵转向依赖于生物合成的发酵，即向代谢产物 大量积累的方向转移。
第三代基因工程。
实用文档
代谢工程的产生
• 微生物发酵已经有几千年的历史，早在2000多年 以前，人们就开始利用微生物进行白酒、黄酒、 葡萄酒、啤酒和清酒等的发酵，此时的发酵被称 为天然发酵时代。
• 20世纪40年代，随着抗生素青霉素的发酵生产的 大规模进行，开始了现代发酵工业时代。通过自 然选择的方法，人们用10-6的突变几率来筛选所谓 的高产菌株。由于没有代谢控制发酵理论作为指 导，直到20世纪60年代现代发酵工业仍处于盲目 阶段。
实用文档
• 代谢控制发酵就是利用遗传学的方法或生 物化学方法，人为地在DNA分子水平上改变 和控制微生物的代谢，使得目的产物大量 的生成、积累的发酵。
• 代谢控制发酵的核心：解除微生物代谢控 制机制，打破微生物正常的代谢调节，人 为地控制微生物的代谢。
实用文档
• 随着代谢控制发酵理论的逐渐完善，目前已发展 出一个重要的研究分支——代谢工程。
• （1）1988年MacQuitty指出，微生物途径工程 (Microbial Pathway engineering)是利用DNA重组 技术修饰各种代谢途径（包括生物体非固有的 代谢途径），提高特定代谢物的产量。
• （ 2 ） 1991 年 Bailey 将 代 谢 工 程 (Metabolic engineering)定义为：利用DNA重组技术优化细 胞的酶活、转运和调控功能，提高细胞活力。
苏氨酸综述
苏氨酸背景苏氨酸，学名为2-氨基-3-羟基丁酸。
是一种含有一个醇式羟基的脂肪族α氨基酸。
其中，L-苏氨酸是组成蛋白质的20种氨基酸中的一种，有两个不对称碳原子，具有4种异构体。
是哺乳动物的必需氨基酸和生酮氨基酸。
它是由Mecoy在1935年于纤维蛋白水解物之中分离和鉴定出来的。
在人体和动物所需的8种必需氨基酸中，苏氨酸是仅次于蛋氨酸、赖氨酸、色氨酸的第4种氨基酸．苏氨酸在人和动物的生长发育中发挥着重要作用，被广泛应用于饲养业、食品业以及医疗业等方面。
L-苏氨酸的生产方法有蛋白质水解法、化学合成法、直接发酵法和酶法。
蛋白质水解法和化学合成法因其存在种种弊端，工业化生产中已经基本不再使用．酶法生产L-苏氨酸具有专一性高、产品单一、易于精制的特点，但所需酶难以获得，制约了酶法的应用。
直接发酵法生产成本低、资源节约、环境污染小，是目前工业化生产L-苏氨酸的主要方式。
自1935年Rose等首次从血纤蛋白中分离到苏氨酸以来，苏氨酸的生产已取得了很大进展。
1950年代，日本的志村、植村2位教授采用添加前体物的方法发酵生产苏氨酸。
国外从1960年代就有开始采用直接发酵法生产L-苏氨酸的报道。
1970年代末，前苏联的研究者们运用基因工程菌规模生产。
世界上主要的苏氨酸生产企业有日本味之素公司、德国德固赛公司、美国ADM公司、日本协合发酵工业公司等。
国内从1982年才开始有L-苏氨酸产生菌选育的报道，黄和容等报道了以钝齿棒杆菌(Corynebacterium crenatum)为出发菌株选育苏氨酸产生菌，产量为13g/L。
1986年，檀耀辉等报道以乳糖发酵短杆菌(Brevibacterium lactofermentum)的出发菌株，选育出1株L-苏氨酸产生菌，在适宜条件下发酵72h可产酸16/L。
目前，国内外均采用基因工程菌进行生产，国外产酸水平为100 g/L左右，国内为80 g/L左右，糖酸转化率为30％-40%。
氨基酸技术发展及新产品开发
参考文献
Krömer J，Sorgenfrei O，Klopprogge K，et al. In-depth profiling of lysine-producing Corynebacterium glutamicum by combined analysis of the transcriptome，metabolome, and fluxome. J Bacteriol，2004，186:1769-1784.
氨基酸衍生物
D- 氨基酸、β- 氨基酸、短肽、 均聚氨基酸
发酵法、酶法转化 化学合成
医药、食品、 材料
参考文献
Dong X，Quinn P J，Wang X. Metabolic engineering of Escherichia coli and Corynebacterium glutamicum for the production of L-threonine. Biotechnol Adv，2011， 29:11-23.
氨基酸技术发展及新产品开发
氨基酸技术发展及新产品开发
谢希贤 陈 宁 （天津科技大学生物工程学院，天津 300457）
doi:10.3969/j.issn.1674-0319.2014.04.004
氨基酸及其衍生物具有非常重要的生理功能。氨基酸工业是发酵工业的 支柱产业之一，其产品有着广泛的应用和巨大的市场。近些年，氨基酸工业 的发展日新月异，各种氨基酸生产的新菌种、新工艺和新技术层出不穷，这 为氨基酸工业的进一步发展提供了巨大的动力。主要介绍氨基酸代谢工程的 技术发展和氨基酸深层次加工及新产品开发进展。
参考文献
Ohnishi J，Mitsuhashi S，Hayashi M，et al. A novel methodology employing Corynebacterium glutamicum genome information to generate a new L-lysine-producing mutant. Appl Microbiol Biotechnol，2002，58:217-223.
维生素B12的微生物工程生产研究进展
维生素B12的微生物工程生产研究进展摘要：维生素B12是种人体必需的维生素，已经广泛地用于医疗及食品行业。
自然界中高等生物均不能合成维生素B12，工业生产中主要依赖少数细菌或者古细菌等的微生物发酵方式获得。
多年来，通过遗传学改造菌株的代谢通路在菌株实际生产过程中极大地提高了产量。
本综述中，我们概述了维生素B12的生物合成及其代谢调控，并从包括合成生物学和代谢工程等多个策略角度全面了解维生素B12的微生物工程生产研究进展。
关键词：维生素B12；微生物工程；发酵工程；前言维生素B12(Vitamin B12)或称钴胺素（Cobalamin），是一类含金属钴离子的B族维生素家族[1]。
分子结构是以钴离子为中心的咕啉环和5,6-二甲基苯并咪唑为碱基组成的胺素类化合物。
维生素B12的发现始于对严重贫血患者的胃分泌物中检测研究，美国内科医生卡斯尔在正常人胃部检测出维生素B12，却无法在恶性贫血病患的胃分泌物中发现。
维生素B12在机体内主要充当辅酶功能，主要参与碳上的氢原子与邻位碳上一个基团之间的交换或者分子间的甲基转移反应，参与人体必需的氨基酸甲硫氨酸的体内循环途径及四氢叶酸的再生等生命活动。
当上述反应受阻，核酸合成发生障碍而导致细胞分裂异常，出现巨幼红细胞性贫血（megaloblastic anemia）[2]，即恶性贫血。
当前工业界生产B12的途径主要是依赖微生物工程，而微生物的B12合成途径主要包括两类即从头合成及补救途径[3]。
微生物从头生物合成维生素B12通过两种代谢途径：在细菌和古菌分别为好氧途径或厌氧途径。
维生素B12也可以通过补救途径利用大肠杆菌进行合成。
但这些菌株具有其自身缺点，例如发酵周期长，发酵复杂而且设备昂贵，培养基要求高以及缺乏优良的遗传体系。
迄今为止，研究者对于维生素B12大多数都集中在传统策略上，例如随机诱变和发酵过程优化，而对代谢工程的研究却很有限。
最近，工程师们将注意力转移到大肠杆菌上，作为生产维生素B12的平台。
代谢工程概述课件
学习交流PPT
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3、研究生物合成机制的常用方法 （1）刺激实验法 （2）同位素示踪法 （3）洗涤菌丝悬浮法 （4）无细胞抽提法 （5）遗传特性诱变法
学习交流PPT
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• 刺激实验法：在发酵培养基中，加入某些可能是 前体的物质，观察该物质在发酵过程中的被利用 情况与促进目的产物生成的效果。
• 洗涤菌丝法（或称静息细胞法）：取不同生长阶 段的菌丝，先洗去沾染的原培养基成分及代谢产 物，然后将菌丝悬浮于人工培养系统内，在一定 条件下继续观察被试验的化合物对菌体代谢和对 产物合成的影响。
学习交流PPT
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• 3、数学及计算机工具：研究代谢工程不仅需要遗 传学知识，而且需要对寄主菌的生化代谢途径和 生理学有深入的理解，所以将DNA数据库的信息 应用于代谢工程并开发出适合的软件系统是十分 必要的，Karp等构建了981个生命体化合物数据库， 为未来的发展奠定了基础。人们已在实验的基础
代谢工程
( Metabolic Engineering )
学习交流PPT
1
第一节 代谢工程概述
现代生物技术手段主要包括：
• 基因工程 (Gene Engineering) • 细胞工程 (Cell Engineering) • 发酵工程 (Fermentation Engineering) • 酶工程 (Enzyme Engineering)
• （1）1988年MacQuitty指出，微生物途径工程 (Microbial Pathway engineering)是利用DNA重 组技术修饰各种代谢途径（包括生物体非固有 的代谢途径），提高特定代谢物的产量。
• （ 2 ） 1991 年 Bailey 将 代 谢 工 程 (Metabolic engineering)定义为：利用DNA重组技术优化细 胞的酶活、转运和调控功能，提高细胞活力。
酵母终止子工程从机理探索到人工设计
2020年第1卷第6期|Syn thetic Bio logy J ournal2020，1（6）：709-721酵母终止子工程：从机理探索到人工设计盛月，张根林（石河子大学化学化工学院，新疆兵团化工绿色过程重点实验室，新疆石河子832003）摘要：生物系统的复杂性为生物元器件的构建提出了挑战，新型控制元件的发现和稳定可调节的元件设计成为合成生物学的重要内容之一。
终止子作为基因元件独立于编码基因行使终止转录的功能，是一种重要的合成生物学控制元件。
研究表明终止子作用有强有弱，终止子的选择会直接影响mRNA 的量，并且随着终止子结构与功能的逐渐清晰和对转录终止机理的深入解析，以短小、可控、可设计为特征的终止子工程得以快速发展。
本文以常规酿酒酵母为基础，系统总结了酿酒酵母中终止子元件在结构发现、功能表征、转录终止机理方面的最新研究进展，并讨论了终止子的人工设计及在途径工程精细调控领域的应用情况，展望了终止子工程面临的挑战、可能的解决途径及在非模式酵母中发展的潜力和意义。
这为研究人员开发合成生物学元件和异源合成途径优化提供了科学的理论参考。
关键词：酿酒酵母；终止子；mRNA 加工；转录终止；代谢途径调控中图分类号：Q81文献标志码：AY east terminator engineering ：from mechanism exploration to artificial designSHENG Yue ，ZHANG Genlin（School of Chemistry and Chemical Engineering ，Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan ，Shihezi University ，Shihezi 832003，Xinjiang ，China ）Abstract:The complexity of biological systems poses challenges for the construction of biological components.The discovery of new control parts and the design of stable and adjustable parts have become one of the important contents of synthetic biology.Acted as a genetic part independently of the coding gene to terminate transcription,a terminator is an important biological part for tuning gene expression when designing synthetic gene networks.The activity of terminator can be strong or weak,thus the choice of terminator will directly affect the amount of mRNA produced.With the gradual clarification of the structure and function on terminator and in-depth analysis of the mechanism of transcription termination,terminator engineering has been rapidly developed to construct shorter,controllable and designable terminators.In this review,the progress about the structural discovery,functional characterization,and收稿日期：2020-02-29修回日期：2020-04-15基金项目：国家自然科学基金（21676167）；兵团中青年科技创新领军人才计划（2017CB007）引用本文：盛月，张根林.酵母终止子工程：从机理探索到人工设计［J ］.合成生物学，2020，1（6）：709-721Citation：SHENG Yue，ZHANG Genlin.Yeast terminator engineering：from mechanism exploration to artificial design ［J ］.Synthetic Biology Journal，2020，1（6）：709-721DOI :10.12211/2096-8280.2020-009特约评述合成生物学第1卷transcription termination mechanism of terminator in Saccharomyces cerevisiae are systematically summarized.The artificial design of terminator and its application in the field of fine regulation of pathway engineering are discussed. The challenges and possible solutions for terminator engineering,potential and significance for developing terminator engineering in non-model yeast are also prospected.This review provides a theoretical guidance for researchers to develop synthetic biological elements and optimization of heterologous synthetic pathways.Keywords:Saccharomyces cerevisiae;terminator;mRNA processing;transcription termination;metabolic pathway regulation合成生物学作为21本世纪一个充满活力的新兴交叉学科，以工程化思想理性设计改造生命体、创造新功能。
Systems Engineering
Systems EngineeringAs a systems engineer, one of the biggest challenges I face is ensuring that all the requirements for a project are met. This involves not only understanding the technical aspects of the system, but also the needs and expectations of the stakeholders involved. It can be a complex and daunting task, as there are often competing priorities and constraints that need to be balanced. Additionally, there is the constant pressure to deliver the project on time and within budget, while also ensuring that the system is reliable, efficient, and meets the needs of the end users. One perspective to consider when approaching requirements in systems engineering is that of the end user. It is essential to understand their needs and expectations in order to design a system that will truly meet their requirements. This involves gathering feedback through interviews, surveys, and usability testing, and using this information to inform the design and development process. By putting the end user at the center of the design process, we can ensure that the system will be intuitive, user-friendly, and ultimately successful in meeting their needs. Another important perspective to consider is that of the stakeholders involved in the project. This can include everyone from project managers and engineers to customers and regulatory bodies. Each stakeholder will have their own set of requirements and expectations for the system, and it is the job of the systems engineer to understand and balance these competing needs. This often involves negotiation and compromise, as well as clear and effective communication to ensure that all stakeholders are on the same page. From a technical perspective, meeting requirements in systems engineering often involves a deep understanding of the underlying technologies and systems involved. This can include everything from software and hardware components to network infrastructure and data management. It is essential to have a strong grasp of these technical aspects in order to design and implement a system that will meet the specified requirements. This may involve conducting thorough research, consulting with subject matter experts, and staying up to date on the latest advancements in the field. In addition to the technical aspects, there are also non-technical requirements to consider, such as regulatory compliance, safety standards, and ethical considerations. These requirements are often just as important as thetechnical ones, and failing to meet them can have serious consequences. As a systems engineer, it is crucial to have a comprehensive understanding of thesenon-technical requirements and to ensure that they are fully integrated into the design and development process. One of the biggest challenges in meeting requirements in systems engineering is the ever-changing nature of technology and the business environment. New technologies are constantly emerging, and customer needs and market demands are always evolving. This means that requirements for a system can change mid-project, and it is the job of the systems engineer to adapt and respond to these changes while still delivering a successful outcome. This requires flexibility, creativity, and the ability to think on your feet in order to meet the evolving requirements of the project. In conclusion, meeting requirements in systems engineering is a multifaceted and challenging task that requires a deep understanding of technical, human, and business perspectives. By considering the needs of end users, stakeholders, and the ever-changing technological and business environment, systems engineers can design and implement systems that truly meet the needs and expectations of all involved. It requires a combination of technical expertise, effective communication, and adaptability in order to successfully navigate the complexities of meeting requirements in systems engineering.。
生物工程的英语单词
生物工程的英语单词英文回答：Bioengineering The application of biologicalprinciples to the design and construction of systems and products.Genetic engineering The alteration of an organism's genetic material to achieve a desired trait or characteristic.Tissue engineering The use of living cells and materials to create new or repair damaged tissues.Biomedical engineering The application of engineering principles to solve problems in medicine and health care.Agricultural biotechnology The use of genetic engineering and other techniques to improve crop yields and livestock production.Environmental biotechnology The use of biological processes to clean up pollution and protect the environment.Synthetic biology The design and construction of new biological systems from scratch.Bioinformatics The use of computational tools to analyze and understand biological data.Systems biology The study of complex biological systems as a whole, rather than focusing on individual components.Metabolic engineering The design and construction of new metabolic pathways to produce desired products.Protein engineering The modification of proteins to improve their function or stability.Immunotherapy The use of the body's immune system to fight disease.Gene therapy The use of genes to treat genetic disorders.中文回答：生物工程将生物学原理应用于系统和产品的设计和建造。
Systems Engineering
Systems EngineeringAs a systems engineer, it is crucial to understand and address the diverse perspectives that come into play when designing and implementing complex systems. One of the key aspects of systems engineering is the ability to consider the needs and requirements of various stakeholders, including end-users, designers, developers, and project managers. By taking into account these different perspectives, a systems engineer can ensure that the final product meets the needs and expectations of all parties involved. From the perspective of end-users, the primary concern is often usability and functionality. End-users want a system that is intuitive to use, reliable, and meets their specific needs. They may not be concerned with the technical details of how the system works, but rather with how it can improve their daily tasks or streamline their workflow. As a systems engineer, it is important to gather feedback from end-users throughout the design process to ensure that the final product meets their expectations. Designers and developers, on the other hand, are more concerned with the technical aspects of the system. They want a system that is efficient, scalable, and easy to maintain. They may be more focused on the underlying architecture and technology stack, as well as ensuring that the system can be easily integrated with other systems or platforms. Systems engineers must work closely with designers and developers to ensure that the system meets their technical requirements while also addressing the needs of end-users. Project managers play a crucial role in the systems engineering process by overseeing the project timeline, budget, and resources. From their perspective, the primary concern is often ensuring that the project is completed on time and within budget. Project managers may be more focused on risk management, resource allocation, and communication with stakeholders. Systems engineers must work closely with project managers to ensure that the project stays on track and that any potential risks are identified and mitigated. In addition to considering the perspectives of end-users, designers, developers, and project managers, systems engineers must also take into account external factors such as regulatory requirements, industry standards, and market trends. Regulatory requirements, such as data privacy laws or industry-specific regulations, may impact the design and implementation of a system. Industry standards, such as ISOor IEEE standards, may also influence the design process by providing guidelines and best practices. Market trends, such as emerging technologies or changing consumer preferences, may also play a role in shaping the design of a system. Systems engineers must stay up-to-date on the latest trends and developments in their field to ensure that the system they are designing remains relevant and competitive. By considering these diverse perspectives and external factors, systems engineers can design and implement systems that meet the needs of all stakeholders and are well-positioned for success in the marketplace.。
Systems Engineering
Systems EngineeringAs a systems engineer, I often encounter various challenges in my line of work. One of the most common problems I face is ensuring that all the requirements of a system are met. This involves understanding the needs of the end-users, as well as the technical specifications that the system must adhere to. It can be a complex and time-consuming process, but it is essential for the successful implementation of any system. One perspective to consider when addressing this problem is theend-user's point of view. Understanding their needs and expectations is crucial in determining the requirements of the system. This involves conducting thorough research, interviews, and surveys to gather relevant data. It also requires empathy and the ability to put oneself in the shoes of the end-users to trulygrasp what they require from the system. This can be a challenging task, as end-users may have diverse and sometimes conflicting needs, but it is essential for creating a system that truly meets their requirements. Another perspective to consider is the technical aspect of the requirements. This involves understanding the capabilities and limitations of the technology that will be used in the system. It requires collaboration with technical experts and stakeholders to ensure that the requirements are feasible and align with the capabilities of the technology. This can be a complex process, as technology is constantly evolving, and it requires staying updated with the latest advancements in the field. It also involves considering factors such as scalability, security, and interoperabilityto ensure that the system meets technical requirements. In addition to the end-user and technical perspectives, it is also crucial to consider the business perspective when addressing system requirements. This involves understanding the business goals and objectives that the system is intended to support. It requires collaboration with business stakeholders to ensure that the requirements alignwith the strategic direction of the organization. This can be a challenging task, as business priorities may change over time, and it requires the ability to adapt and align the system requirements accordingly. Furthermore, the regulatory and compliance perspective is also important to consider when addressing system requirements. Depending on the industry and the nature of the system, there may be various regulations and standards that the system must adhere to. This requires adeep understanding of the regulatory landscape and collaboration with legal and compliance experts to ensure that the system meets all the necessary requirements. This can be a complex and time-consuming process, as regulations are constantly evolving, and it requires staying updated with the latest changes in the regulatory environment. Moreover, the project management perspective is also crucial when addressing system requirements. This involves managing the requirements gathering process within the constraints of time, budget, and resources. It requires effective communication and collaboration with various stakeholders to ensure that the requirements are clearly documented, understood, and agreed upon. It also involves prioritizing requirements and managing changes throughout the project lifecycle. This can be a challenging task, as requirements may evolve over time, and it requires the ability to adapt and manage changes effectively. In conclusion, addressing system requirements as a systems engineer involves considering multiple perspectives, including the end-user, technical, business, regulatory, and project management perspectives. It requires empathy, technical expertise, collaboration, and effective communication to ensure that the system requirements are clearly defined, understood, and met. While it can be a complex and challenging process, it is essential for the successful implementation of any system.。
Systems Engineering
Systems EngineeringAs a systems engineer, I often encounter various problems that require careful analysis and innovative solutions. One of the most common issues I face is the challenge of managing complex requirements from multiple stakeholders. This can be a daunting task, as different parties often have conflicting needs and priorities. Balancing these requirements while ensuring the overall system integrity and functionality is a delicate process that requires a deep understanding of the system and effective communication skills. Another problem that I frequently encounter is the need to integrate new technologies into existing systems. This can be a challenging task, as it requires a thorough understanding of both the existing system and the new technology, as well as the ability to identify potential conflicts and risks. It also requires effective planning and coordination to ensure a smooth integration process without disrupting theexisting system's operations. Furthermore, ensuring the reliability and safety of complex systems is a constant concern for systems engineers. This involves identifying potential failure points, developing robust testing procedures, and implementing effective maintenance and monitoring protocols. The consequences of system failures can be severe, so it is essential to approach this problem with the utmost care and attention to detail. In addition to technical challenges, systems engineers often face interpersonal and organizational problems. This can include navigating conflicting personalities and priorities among team members, as well as managing expectations and demands from various stakeholders. Effective leadership and communication skills are crucial in addressing these challenges and fostering a collaborative and productive work environment. Moreover, as systems become increasingly interconnected and interdependent, cybersecurity has emerged as a critical concern for systems engineers. Protecting sensitive data and ensuring the integrity of systems against cyber threats requires a proactive and multi-faceted approach that involves both technical solutions and organizational policies. Finally, the rapid pace of technological advancement presents a constant challenge for systems engineers. Keeping up with the latest developments and incorporating relevant innovations into existing systems requires continuous learning and adaptation. It also involves anticipating future needs and trends toensure that systems remain relevant and effective in the long term. In conclusion, systems engineering presents a wide range of complex and multifaceted problemsthat require a combination of technical expertise, interpersonal skills, and strategic thinking to address. By approaching these challenges with creativity, resilience, and a commitment to continuous improvement, systems engineers can develop innovative solutions that drive progress and ensure the reliability and functionality of critical systems.。
Systems Engineering and Design
Systems Engineering and Design As a systems engineer, I am constantly faced with the challenge of designing and integrating complex systems to meet the needs of various stakeholders. This requires a deep understanding of the requirements and constraints of the system,as well as the ability to balance competing demands to achieve an optimal solution. One of the key challenges in systems engineering is the need to manage andmitigate risks throughout the entire lifecycle of a project. This involves identifying potential hazards, assessing their likelihood and impact, and developing strategies to minimize their effects. From a technical perspective, systems engineers must have a strong grasp of a wide range of engineering disciplines, including mechanical, electrical, and software engineering. This multidisciplinary approach is essential for understanding how different components of a system interact and affect each other. It also requires a keen awareness of the latest technological developments and an ability to apply them to solve real-world problems. This can be both exciting and daunting, as it requires constant learning and adaptation to stay at the forefront of the field. Another aspect of systems engineering that is often overlooked is the human element. Systems are ultimately designed to be used by people, and their success depends on how well they meet the needs and expectations of their users. This requires a deep understanding of human factors, such as cognitive psychology, ergonomics, and user experience design. It also involves effective communication and collaboration with stakeholders to ensure that their voices are heard and their concerns are addressed. In addition to technical and human factors, systems engineers mustalso consider the broader social, economic, and environmental impacts of their work. This involves thinking about the long-term sustainability of a system, its potential effects on different communities, and its overall cost-effectiveness. It also requires a commitment to ethical decision-making and a willingness to advocate for responsible and inclusive design practices. One of the mostrewarding aspects of systems engineering is the opportunity to see the tangible impact of your work. Whether it's designing a new medical device that improves patient outcomes, optimizing a transportation system to reduce carbon emissions,or creating a more intuitive user interface for a software application, systemsengineers have the power to make a real difference in the world. This sense of purpose and the opportunity to contribute to meaningful projects is what motivates many of us to continue pushing the boundaries of what is possible. However, with great power comes great responsibility. The complexity and interconnectedness of modern systems mean that even small errors or oversights can have far-reaching consequences. This can create a significant amount of pressure and stress for systems engineers, who must constantly strive for perfection while navigatingtight deadlines and limited resources. It's important for us to recognize the toll that this can take on our mental and emotional well-being, and to prioritize self-care and support from our colleagues and mentors. In conclusion, systems engineering is a multifaceted and demanding field that requires a combination of technical expertise, human-centered design, and a strong ethical compass. While it presents numerous challenges, it also offers the opportunity to make a meaningful impact on the world and to constantly learn and grow as a professional. By embracing these complexities and striving for excellence, systems engineers can help create a better future for all.。
Manufacturing Systems Engineering
Manufacturing Systems Engineering Manufacturing Systems Engineering is a multidisciplinary field that combines principles of engineering, management, and technology to design, analyze, and optimize manufacturing systems. It plays a crucial role in the development and improvement of manufacturing processes, ensuring efficiency, quality, and cost-effectiveness. One perspective to consider in Manufacturing Systems Engineering is the technological aspect. With the rapid advancement of technology, manufacturing systems have become more complex and interconnected. Automation, robotics, and artificial intelligence have revolutionized the way manufacturing processes are carried out. These technologies have enabled faster production, improved accuracy, and reduced human error. However, they have also raised concerns about job displacement and the need for upskilling the workforce to adapt to these changes. Another perspective to consider is the economic aspect. Manufacturing systems engineering aims to improve the productivity andprofitability of manufacturing processes. By optimizing the use of resources, reducing waste, and streamlining operations, manufacturing systems engineers can help companies achieve cost savings and increase their competitiveness in the market. However, implementing changes in manufacturing systems can be costly, requiring investments in new equipment, training, and infrastructure. Balancing the upfront costs with the long-term benefits is a key consideration in decision-making. The environmental perspective is also important in manufacturing systems engineering. The manufacturing industry is a significant contributor to environmental pollution and resource depletion. Manufacturing systems engineers can play a crucial role in designing sustainable manufacturing processes that minimize waste generation, energy consumption, and carbon emissions. This can be achieved through the adoption of cleaner technologies, recycling and reuse strategies, and the integration of renewable energy sources. By prioritizing environmental sustainability, manufacturing systems engineering can contribute to the overall goal of achieving a more sustainable and greener future. From a management perspective, manufacturing systems engineering involves coordinating and optimizing various elements of the manufacturing system, including personnel, equipment, materials, and information flow. Effective management of these elementsis essential to ensure smooth operations, timely delivery of products, and customer satisfaction. Manufacturing systems engineers need to have strong leadership and communication skills to collaborate with different stakeholders, including production managers, engineers, technicians, and suppliers. They also need to be able to analyze data, identify bottlenecks, and make informed decisions to improve the overall efficiency and effectiveness of the manufacturing system. In conclusion, Manufacturing Systems Engineering is a multidimensional field that encompasses technological, economic, environmental, and management perspectives. It requires a holistic approach to designing, analyzing, and optimizing manufacturing systems to ensure efficiency, quality, and sustainability. By considering multiple perspectives, manufacturing systems engineers can make informed decisions that balance the needs of the company, the workforce, and the environment. With the continuous advancement of technology and the increasing focus on sustainability, the role of manufacturing systems engineering will continue to evolve and play a crucial role in shaping the future of manufacturing.。
Systems Engineering
Systems EngineeringSystems engineering is an interdisciplinary field of engineering that focuses on the design, development, and management of complex systems. These systems can range from simple products like a toaster to complex systems like an aircraft or a power plant. The main goal of systems engineering is to ensure that the system functions efficiently, reliably, and safely. In this essay, we will discuss the importance of systems engineering and its various perspectives. The first perspective of systems engineering is the technical perspective. This perspective focuses on the technical aspects of the system, including its design, development, and testing. Systems engineers in this perspective use various tools and techniques to ensure that the system meets the requirements and specifications. They work closely with other engineers, designers, and stakeholders to ensure that the system is designed and developed to meet the needs of the users. The second perspective of systems engineering is the management perspective. This perspective focuses on the management of the system, including its planning, scheduling, and budgeting. Systems engineers in this perspective work closely with project managers and other stakeholders to ensure that the system is developed within the allocated time and budget. They also ensure that the system meets the quality standards and that the risks associated with the system are managed effectively. The third perspective of systems engineering is the user perspective. This perspective focuses on the needs and requirements of the users of the system. Systems engineers in this perspective work closely with the users to understand their needs and requirements and to ensure that the system is designed and developed to meet those needs. They also ensure that the system is user-friendly and easy to use. The fourth perspective of systems engineering is the safety perspective. This perspective focuses on the safety of the system, including its operation, maintenance, and disposal. Systems engineers in this perspective work closely with safety experts to ensure that the system is designed and developed to be safe to operate. They also ensure that the system is maintained properly and that it is disposed of safely at the end of its life. The fifth perspective of systems engineering is the environmental perspective. This perspective focuses on the environmental impact of the system, including its energy consumption,emissions, and waste generation. Systems engineers in this perspective workclosely with environmental experts to ensure that the system is designed and developed to be environmentally friendly. They also ensure that the system is operated in an environmentally responsible manner and that its waste is disposedof safely. In conclusion, systems engineering is an important field ofengineering that focuses on the design, development, and management of complex systems. It is an interdisciplinary field that requires expertise in various areas, including engineering, management, and environmental science. The various perspectives of systems engineering, including technical, management, user, safety, and environmental, ensure that the system is designed and developed to meet the needs of the users while being safe, reliable, and environmentally friendly. Systems engineering is essential for the development of complex systems and is critical for the success of many industries, including aerospace, defense, and energy.。
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• Further investigation is warranted to address the challenges for promising commercialization.
That's all
Thank you!
• The OptForce computational protocol was used for arriving at suggestions for strain redesign by identifying the minimal set of reactions that need to be actively manipulated to guarantee an imposed production yield.
Bioenergy Process Engineering
Name : Ashly Student ID : X
Systems Metabolic Engineering Design: Fatty Acid Production as an Emerging Case Study (Ting Wei Tee, Anupam Chowdhury,
• Synthetic biology also expands the capacity of host strains to produce heterologous chemicals, and optimizes the synthetic pathway by improving translation efficiency and optimizing biological circuit
Conclusion and Future Challenges
• Classical metabolic engineering, integrated computational/experimental approach, and synthetic biology have contributed towards the improved production of FAs in E. coli, and could be extended to the development of cell factories for specific chemical production.
• In this review, we describe a classical metabolic engineering technique, an integrated experimental and computational strategy, and a synthetic engineerห้องสมุดไป่ตู้ng effort for enhancing fatty acid production in E. coli.
• Computational strain design protocols consider the complex interconnectivity of cellular metabolism including cofactor balances to identify key metabolic bottlenecks towards the production of a chemical, and predict (often non-intuitive) strategies to overcome them.
Integrated Computational and Experimental Approach
• Even though metabolic engineering has taken long strides in manipulating the metabolic network towards the overproduction of a desired chemical, the process is hampered by bottlenecks of time and accuracy.
• Here we highlight a rational strain design process in systems biology, an integrated computational and experimental approach for carboxylic acid production, as an alternative method.
Costas D. Maranas,Jacqueline V. Shanks)
• Department of Chemical and Biological Engineering, Iowa State University, Ames, Iowa; • Department of Chemical Engineering, Pennsylvania State University, University Park,Pennsylvania
• The abundance of genetic information available for E.coli specifically, fatty acid metabolism in E.coli, supports this bacterium as a promising host for engineering a biocatalyst for the microbial production of fatty acids.
My opinion
• The metabolic engineering design process has evolved into a Systems Metabolic Engineering design process. • Systems Metabolic Engineering encompasses systems biology, synthetic biology, and evolutionary engineering at the system level, provides powerful techniques to design new biocatalysts .
Synthetic Biology
• Synthetic biology plays a crucial role in modeling, understanding, and fine-tuning the core components in metabolic pathways. • Engineering core pieces of metabolic pathways helps meet specified performance criteria, such as gaining desired phenotypes, once they are integrated into larger biological systems.
Classical Metabolic Engineering
• Classical metabolic engineering involves an iterative process of synthesis and analysis, where increasingly refined strains are designed and constructed based on the past knowledge. Several strategies have been employed to improve FA production.
• In addition, acyl-ACP thioesterase, catalyzing the terminal reaction to produce free FAs, is crucial in controlling metabolic flux towards FA. • The synergy of the above positive method is often used to significantly boost FA production.
• Recent successes rooted in different features of systems metabolic engineering in the strain design of high-yielding medium chain fatty acid producing E.coli provide an emerging case study of design methods for effective strain design.
ABSTRACT:
• Increasing demand for petroleum has stimulated industry to develop sustainable production of chemicals and biofuels using microbial cell factories. • Fatty acids of chain lengths from C6 to C16 are propitious intermediates for the catalytic synthesis of industrial chemicals and diesel-like biofuels.