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Towards engineering and production of artificial spider silk using tools of synthetic biology 利用合成生物学的工具进行人造蜘蛛丝的工程和生产
Engineering biology Pub Date : 2020-03-16 DOI: 10.1049/enb.2019.0017
Hashwardhan Poddar, Rainer Breitling, Eriko Takano
{"title":"Towards engineering and production of artificial spider silk using tools of synthetic biology","authors":"Hashwardhan Poddar,&nbsp;Rainer Breitling,&nbsp;Eriko Takano","doi":"10.1049/enb.2019.0017","DOIUrl":"10.1049/enb.2019.0017","url":null,"abstract":"<div>\u0000 <p>Spider silk is one of the strongest biomaterials available in nature. Its mechanical properties make it a good candidate for applications in various fields ranging from protective armour to bandages for wound dressing to coatings for medical implants. Spider silk is formed by an intricate arrangement of spidroins, which are extremely large proteins containing long stretches of repeating segments rich in alanine and glycine. A large amount of research has been directed towards harnessing the spectacular potential of spider silks and using them for different applications. The interdisciplinary approach of synthetic biology is an ideal tool to study these spider silk proteins and work towards the engineering and production of synthetic spider silk. This review aims to highlight the recent progress that has been made in the study of spider silk proteins using different branches of synthetic biology. Here, the authors discuss the different computational approaches, directed evolution techniques and various expression platforms that have been tested for the successful production of spider silk. Future challenges facing the field and possible solutions offered by synthetic biology are also discussed.</p>\u0000 </div>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"4 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2020-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1049/enb.2019.0017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9192455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Machine learning-driven protein engineering: a case study in computational drug discovery 机器学习驱动的蛋白质工程:计算药物发现的案例研究
Engineering biology Pub Date : 2020-03-16 DOI: 10.1049/enb.2019.0019
Harry F. Rickerby, Katya Putintseva, Christopher Cozens
{"title":"Machine learning-driven protein engineering: a case study in computational drug discovery","authors":"Harry F. Rickerby,&nbsp;Katya Putintseva,&nbsp;Christopher Cozens","doi":"10.1049/enb.2019.0019","DOIUrl":"10.1049/enb.2019.0019","url":null,"abstract":"<div>\u0000 <p>Research and development in drug discovery will need to find significant efficiency gains if the industry is to continue generating novel drugs. There is great expectation for machine learning (ML) to provide this boost in R&amp;D productivity, but to harness the full potential of ML, the generation of new, high-quality datasets will be necessary. Here, the authors present a platform that combines high-throughput display and selection data generation with ML. More specifically, deep learning is used to inform the directed evolution of novel biotherapeutics using DNA library synthesis, ultra-high throughput selections, and next generation sequencing. By combining the learnings of multiple <i>in silico</i> models, their platform enables multi-parameter optimisation across multiple important protein characteristics. They also present a model for benchmarking these ML-driven drug discovery platforms according to the accuracy of their underlying <i>in silico</i> models, in conjunction with the throughput of their empirical experimentation.</p>\u0000 </div>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"4 1","pages":"7-9"},"PeriodicalIF":0.0,"publicationDate":"2020-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1049/enb.2019.0019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9192460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Engineered gene networks enable non-genetic drug resistance and enhanced cellular robustness 工程基因网络使非遗传耐药性和增强细胞稳健性成为可能
Engineering biology Pub Date : 2019-11-07 DOI: 10.1049/enb.2019.0009
Brendan Camellato, Ian J. Roney, Afnan Azizi, Daniel Charlebois, Mads Kaern
{"title":"Engineered gene networks enable non-genetic drug resistance and enhanced cellular robustness","authors":"Brendan Camellato,&nbsp;Ian J. Roney,&nbsp;Afnan Azizi,&nbsp;Daniel Charlebois,&nbsp;Mads Kaern","doi":"10.1049/enb.2019.0009","DOIUrl":"10.1049/enb.2019.0009","url":null,"abstract":"<div>\u0000 <p>Drug resistance complicates the treatment of cancer and infectious diseases, and often arises from the elevated expression of a gene that neutralises or reduces drug activity. To investigate this and other expression-based mechanisms of drug resistance, the authors engineered a set of gene regulatory networks in the eukaryotic model organism <i>Saccharomyces cerevisiae</i> to control a homologue of the cancer-related human multidrug resistance gene <i>MDR1</i>. Using this system, they explored experimentally how different gene regulatory network features, also called genetic network motifs, contribute to gene expression dynamics and cellular fitness. They observed that coherent feedforward and positive feedback motifs enable rapid and self-sustained activation of gene expression, and enhance cell survival in the presence of a cytotoxic drug. These observations underscore that genetic network motifs can be critical for drug resistance and that genetic network engineering can be used to enhance cellular tolerance to cytotoxins or other environmental stresses.</p>\u0000 </div>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"3 4","pages":"72-79"},"PeriodicalIF":0.0,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/enb.2019.0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48050314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
Large-scale-free network organisation is likely key for biofilm phase transition 大规模的无网络组织可能是生物膜相变的关键
Engineering biology Pub Date : 2019-09-12 DOI: 10.1049/enb.2019.0012
Kumar Selvarajoo
{"title":"Large-scale-free network organisation is likely key for biofilm phase transition","authors":"Kumar Selvarajoo","doi":"10.1049/enb.2019.0012","DOIUrl":"https://doi.org/10.1049/enb.2019.0012","url":null,"abstract":"<div>\u0000 <p>Non-linear Kuramoto model has been used to study synchronised or <i>sync</i> behaviour in numerous fields; however, its application in biology is scarce. Here, the basic model has been introduced and examples where large-scale small-world or scale-free networks are crucial for spontaneous <i>sync</i> have been provide even for low coupling strength. This information was next checked for relevance in living systems where it is now well known that biological networks are scale-free. A recent transcriptome-wide data analysis of a <i>Saccharomyces cerevisiae</i> biofilm showed that low- to middle-expressed genes are key for scale invariance in biology. Together, the current data indicate that a biological network connectivity structure with low coupling strength, or expression levels, is sufficient for <i>sync</i> behaviour. For biofilm regulation, it may, therefore, be necessary to investigate large-scale low-expression genes rather than small-scale high-expression genes.</p>\u0000 </div>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"3 4","pages":"67-71"},"PeriodicalIF":0.0,"publicationDate":"2019-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/enb.2019.0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91830326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineering solventogenic clostridia for commercial production of bio-chemicals 用于生物化学商业化生产的工程溶剂型梭菌
Engineering biology Pub Date : 2019-07-24 DOI: 10.1049/enb.2019.0008
Nathan W. G. Fairhurst, Rachel A. Harper, Holly K. Smith, Lee C. Speight, Joseph S. Clements II, Elizabeth R. Jenkinson
{"title":"Engineering solventogenic clostridia for commercial production of bio-chemicals","authors":"Nathan W. G. Fairhurst,&nbsp;Rachel A. Harper,&nbsp;Holly K. Smith,&nbsp;Lee C. Speight,&nbsp;Joseph S. Clements II,&nbsp;Elizabeth R. Jenkinson","doi":"10.1049/enb.2019.0008","DOIUrl":"10.1049/enb.2019.0008","url":null,"abstract":"<div>\u0000 <p>The manufacture of bio-chemicals through the use of microbial fermentation and renewable feedstock has a number of well-known advantages linked to sustainability and reduced impacts on the environment. Markets for molecules produced with greener credentials are growing as consumers become more aware of what is in the formulated products they use every day. The use of solventogenic clostridia has now been re-commercialised for the production of bio-acetone and bio-n-butanol. The different impurity profiles of these bio-based molecules compared with petro-versions results in performance advantages in downstream derivatisation chemistry, giving an added benefit alongside sustainability advantages. Advances in genome editing now enable us to take the benefits observed with clostridial fermentation and apply them to the production of the next generation of bio-molecules.</p>\u0000 </div>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"3 3","pages":"41-45"},"PeriodicalIF":0.0,"publicationDate":"2019-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/enb.2019.0008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42435254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Characterisation of Constitutive Promoters from the Anderson library in Chromobacterium violaceum ATCC 12472 紫色色杆菌ATCC 12472 Anderson文库组成启动子的鉴定
Engineering biology Pub Date : 2019-07-12 DOI: 10.1049/enb.2018.5007
Lu Ting Liow, Maybelle Darlene Kho Go, Wen Shan Yew
{"title":"Characterisation of Constitutive Promoters from the Anderson library in Chromobacterium violaceum ATCC 12472","authors":"Lu Ting Liow,&nbsp;Maybelle Darlene Kho Go,&nbsp;Wen Shan Yew","doi":"10.1049/enb.2018.5007","DOIUrl":"10.1049/enb.2018.5007","url":null,"abstract":"<p><i>Chromobacterium violaceum</i> is a potential industrially relevant chassis due to its cyanogenic properties and diverse metabolic energetics. However, its application in synthetic biology is limited by the lack of characterised genetic parts. Six constitutive promoters of a 100-fold range in gene expression from the Anderson library were characterised in <i>C. violaceum</i> using an automated microplate reader. The datasheet provides an insight to the highly similar trend in promoter strengths in <i>C. violaceum</i> to the original characterised strengths of the Anderson library constitutive promoters in <i>E. coli</i>. This provides a foundation for constitutive promoters of different strengths as parts to be used for synthetic biology genetic constructs in <i>C. violaceum</i>.</p>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"3 3","pages":"57-66"},"PeriodicalIF":0.0,"publicationDate":"2019-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1049/enb.2018.5007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45706795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Characterisation of the bacterial biosensor GMG in E-coli BL21 (DE3) 细菌生物传感器GMG在大肠杆菌BL21（DE3）中的表征
Engineering biology Pub Date : 2019-07-10 DOI: 10.1049/enb.2018.5006
Rashmi Rajasabhai, Maybelle Kho Go, Yew Wen Shan
{"title":"Characterisation of the bacterial biosensor GMG in E-coli BL21 (DE3)","authors":"Rashmi Rajasabhai,&nbsp;Maybelle Kho Go,&nbsp;Yew Wen Shan","doi":"10.1049/enb.2018.5006","DOIUrl":"10.1049/enb.2018.5006","url":null,"abstract":"<p>In this work, a gold biosensor has been constructed and characterised in <i>Escherichia coli</i> (<i>E. coli</i>). Though gold biosensors have been previously reported, a NOT gate gold biosensing genetic circuit was constructed using an orthogonal inverter system as an alternative to a circuit where output is contingent solely on input. This enables the detection of changes in gold concentration whereby circuit remains OFF in presence of inducer and ON in absence of inducer. The proposed biosensor is an alternative to conventional forms of gold detection such as Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The constructed biosensor is a collection of components – <i>golTSB</i> operon (isolated from <i>Salmonella enterica</i>), <i>mf</i>-Lon protease (isolated from <i>Mesoplasma florum</i>) and associated ssrA degradation tag with GFP acting as a reporter. The minimum time and concentration required by the biosensor gol-<i>mf</i>lon-GFP (GMG) to achieve the ON output is characterised here using plate reader data derived from a single multi-stage assay.</p>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"3 3","pages":"46-56"},"PeriodicalIF":0.0,"publicationDate":"2019-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1049/enb.2018.5006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44956017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Genome-scale model of C. autoethanogenum reveals optimal bioprocess conditions for high-value chemical production from carbon monoxide C.autoethanogenum的基因组规模模型揭示了利用一氧化碳生产高价值化学品的最佳生物工艺条件
Engineering biology Pub Date : 2019-06-20 DOI: 10.1049/enb.2018.5003
Rupert O.J. Norman, Thomas Millat, Sarah Schatschneider, Anne M. Henstra, Ronja Breitkopf, Bart Pander, Florence J. Annan, Pawel Piatek, Hassan B. Hartman, Mark G. Poolman, David A. Fell, Klaus Winzer, Nigel P. Minton, Charlie Hodgman
{"title":"Genome-scale model of C. autoethanogenum reveals optimal bioprocess conditions for high-value chemical production from carbon monoxide","authors":"Rupert O.J. Norman,&nbsp;Thomas Millat,&nbsp;Sarah Schatschneider,&nbsp;Anne M. Henstra,&nbsp;Ronja Breitkopf,&nbsp;Bart Pander,&nbsp;Florence J. Annan,&nbsp;Pawel Piatek,&nbsp;Hassan B. Hartman,&nbsp;Mark G. Poolman,&nbsp;David A. Fell,&nbsp;Klaus Winzer,&nbsp;Nigel P. Minton,&nbsp;Charlie Hodgman","doi":"10.1049/enb.2018.5003","DOIUrl":"10.1049/enb.2018.5003","url":null,"abstract":"<div>\u0000 <p><i>Clostridium autoethanogenum</i> is an industrial microbe used for the commercial-scale production of ethanol from carbon monoxide. While significant progress has been made in the attempted diversification of this bioprocess, further improvements are desirable, particularly in the formation of the high-value platform chemicals such as 2,3-butanediol (2,3-BD). A new, experimentally parameterised genome-scale model of <i>C. autoethanogenum</i> predicts dramatically increased 2,3-BD production under non-carbon-limited conditions when thermodynamic constraints on hydrogen production are considered.</p>\u0000 </div>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"3 2","pages":"32-40"},"PeriodicalIF":0.0,"publicationDate":"2019-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1049/enb.2018.5003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43506618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 20
Future-proofing synthetic biology: educating the next generation 未来的合成生物学:教育下一代
Engineering biology Pub Date : 2019-06-17 DOI: 10.1049/enb.2019.0001
Jennifer S. Hallinan, Anil Wipat, Richard Kitney, Simon Woods, Ken Taylor, Angel Goñi-Moreno
{"title":"Future-proofing synthetic biology: educating the next generation","authors":"Jennifer S. Hallinan,&nbsp;Anil Wipat,&nbsp;Richard Kitney,&nbsp;Simon Woods,&nbsp;Ken Taylor,&nbsp;Angel Goñi-Moreno","doi":"10.1049/enb.2019.0001","DOIUrl":"10.1049/enb.2019.0001","url":null,"abstract":"<div>\u0000 <p>Synthetic biology is a relatively young field, although it builds upon disciplines whose roots go back centuries. Recently, its practitioners have tended to move into the field out of interest or by chance, and come from a wide variety of backgrounds. It is also a very fast-moving field; new protocols, laboratory equipment, computational facilities and algorithms are being developed at a rapid pace. Students who start studying synthetic biology at an undergraduate or postgraduate level will, in the course of their careers, work with technologies as yet undreamt of, and will do so mostly in the context of highly interdisciplinary teams. In this study, the authors identify some of the key areas required for the education of new synthetic biologists to equip them with both adequate background and sufficient flexibility to tackle these challenges and therefore to future-proof synthetic biology.</p>\u0000 </div>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"3 2","pages":"25-31"},"PeriodicalIF":0.0,"publicationDate":"2019-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1049/enb.2019.0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47858509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Synthetic biology – pathways to commercialisation 合成生物学——商业化的途径
Engineering biology Pub Date : 2019-03-18 DOI: 10.1049/enb.2018.5009
Lionel J. Clarke
{"title":"Synthetic biology – pathways to commercialisation","authors":"Lionel J. Clarke","doi":"10.1049/enb.2018.5009","DOIUrl":"10.1049/enb.2018.5009","url":null,"abstract":"<div>\u0000 <p>Synthetic biology is transforming the ability to manufacture increasingly needed bio-based products in response to rising market demand. By applying engineering principles to the convolution of recent advances in genomic engineering techniques, information technology and automation, synthetic biology is facilitating the replacement of time-consuming ‘discover and grow’ approaches by more precise and affordable ‘biodesign and biomanufacture’ processes. Meantime, societal awareness of specific health, well-being, and environmental issues is increasing ‘market pull’ that will shape future pathways to commercialisation. Market interests will not only shape targets for product function and cost but also increasingly question their provenance. Sustainability concerns are already driving demand to replace petrochemical-derived by bio-derived products, but many established industries wishing to transition may lack familiarity with bio-manufacturing processes and with the wider issues associated with large-scale bio-feedstock supply chains. Meantime, commercialisation of synthetic biology today is being advanced mostly via start-ups and SMEs. Combining the knowledge and skills required to respond to market interests, as the scale of operations and complexity of issues expands, is likely to stimulate an increasing diversity of collaborative approaches.</p>\u0000 </div>","PeriodicalId":72921,"journal":{"name":"Engineering biology","volume":"3 1","pages":"2-5"},"PeriodicalIF":0.0,"publicationDate":"2019-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1049/enb.2018.5009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44815970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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