Synthetic Biology: An Engineering Life
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Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Synthetic Biology is a science dealing with designing new biological devices and systems and also redesigning the existing natural biological system as green technologies that can act as alternatives for various chemical and petroleum industries. It is an interdisciplinary area that basically utilizes engineering principles to modify the existing organisms or altogether make a novel one for conventional biological research. Synthetic biology is a multidisciplinary zone of exploration that seeks to construct new biological fragments, devices, and systems, or to reshape systems that are at present found in nature. This new branch of science has contributed significantly to human health, the environment, basic life science and pharmaceutical science and many more. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. Synthetic biology technologies are budding, fetching the way that almost everything can be contrived sustainably and competitively. Industries must learn to utilize syn-bio to grow new products and methods, improve on the existing ones, and lessen the costs to remain viable in the upcoming times. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.
1. Introduction
Experts have said that the 21st century will be a century of the life sciences. But until recently, the national security community has often overlooked both the biological sciences and biotechnology. In the post-pandemic world, however, the national security community will need to rethink its biosecurity strategy and emerging technology like synthetic biology will play a critical role. Synthetic biologists use engineering principles to design, build and manufacture biological systems and products. In this field, engineers think about biology as code and just like software code engineers can read, write and edit genetic code. In 2016, James Clapper, director of Nation Intelligence suggested that gene editing technology like CRISPR should be considered a weapon of mass destruction (Andrianantoandro et al., 2006). Opportunities also exist to elaborate this technology for good. For example, scientists today are using synthetic biology to intentionally design coronavirus vaccines. Synthetic biology capabilities can also be used to manufacture food, fuel, medicines and other materials like spider silk. Spider silk is lightweight and strong and could one day be used as body Armor and hence is an interest in U S Army. Kraig Bio craft Laboratories in the US produces genetically engineered spider silk at large scales for a wide range of utilization in the military. More broadly, synthetic biology is an emerging driver of the rolling economy, which according to the national academies makes 5% of the US best domestic products that are over 900 billion dollars (Cheng and Lu, 2012). As economic and national security are increasingly entwined and shaped by technology, Synthetic Biology is poised to emerge as a critical enabler of both economic competitiveness and feature national and health security. Synthetic Biology is the next step revolution of genomics and proteomics. In the life science industry, it provides solutions to them so that they can do experiments for rational purposes. It is the inner section of the life sciences, the information sciences and the engineering disciples.
1.1 Biology and synthetic biology – what is the difference
Biology understands living organisms in all their aspects. Biology often uses observations to study the behaviour of any living organism. For example, bacteria use flagella to search for nutrients in their proximity. The spiral movement of the flagella propels the movement in a particular direction (Chappell et al., 2015). So observation is a critical tool that a biologist can use. Another tool understands from creating mutations, mutations are the changes which are made at the DNA level. The third important step that biology uses is anatomic dissection to study how the internal organs behave and work in any organism. Biologists are also inclined towards genetic dissection to study the whole genetic plan of a body, and how DNA interact towards the functioning of the organism. To study DNA one must find out the gene sequence which is base by base the genomic sequence. This is performed by various sequencing strategies including the latest nest generation (fast and cost-effective) DNA sequencing methods. In the end, we get the entire read of the genetic makeup of an organism. Now the real goal of molecular biologists is to understand what this sequence means. How can this be an important plan for living organisms? This is answered by performing sequence analysis (Heinemann and Panke, 2006). Sequence analysis is to gaze into the sequence and do an analysis of the important features that the sequence can contain for proteins, RNA, and reading frame for signals on DNA that are important to direct the protein to read the instructions and forms the part that the cell is in need, transcription factor binding sites, promoter signals and many more. This is where biology ends, and synthetic biology starts. Synthetic biology tries to interpret this sequence in a schematic way (Xiong et al., 2008). One of the concepts of synthetic biology is to decompose the DNA sequence into its biological parts (DNA or Protein), converting the DNA sequence into circuits. For a synthetic biologist, a simple DNA sequence is a circuit of coding regions, promoters, signals for ribosomes, a binding site a regulator protein and a terminator sequence. We can go from sequence to the parts and can study the parts and then we can put them back together in different ways (Sachan et al., 2017). Now the second concept that is very important for synthetic biology is rules and models. So Synthetic biologists just do not want to dissect the sequence to know the exact As, Cs, Gs and Ts or the genome of the organism or the part of the DNA that we want to construct but how does the DNA sequence work together, which are the rules that the cell is following in order to make this part of the sequence functional (Anderson et al., 2006). For this synthetic biology uses some rules which could be some logic rules like a gene is on or a gene is off, it can also be model (mathematical model) that tries to predict how a particular stretch of DNA, promoters, and binding sites are working for the cell. So, rules are basically the steps for the circuit to follow and execute the function. These rules could be put up in some mathematical models which will further predict what to do. The third concept of synthetic biology is standards (people from different laboratories and different industries can work on the same parts) for example stands for gene expressions (Das et al., 2019).
1.2 What is synthetic biology hoping to achieve?
There are two main things that synthetic biology is on tenterhooks to reach –
2. Research activities in synthetic biology
Current research activity in synthetic biology goes consequently in all directions;
2.1 Standard Parts and methods: making standardized parts, making new models, and trying to come up with complex engineering strategies to put its parts together.
2.2 DNA synthesis and design of genomes or genome parts: Previously in genetic engineering it was difficult, cumbersome and took a lot of time to make mutations but now companies have started DNA synthesis. The Biologist will simply write down their sequences, and send them through the computer to a DNA synthesis company that will make the construct which will facilitate large lead to put parts together in a particular way. So consequently, people try to design the whole genome which is a challenging task because we do not understand all the rules very well to be able to put the genome together (Salis et al., 2009).
2.3 Minimal cells and host production platforms: One can make bacteria of yeast that is just chassis, needed to make a motor for the cell and everything else could be just plugged in. So, people often think that the living being that exists naturally is way too complex. They contain viruses, and bacteria and that is why they want to design minimal cells devoid of all the parts which are not needed.
2.4 Protocells and artificial life: There is a huge interest and to try and understand where life is coming from. We do not know but synthetic biologists may be able to recreate certain life forms that would help to understand where life is coming from and what the different paths can lead to life.
2.5 Xeno DNA Biology: Synthetic biologists can alter DNA and proteins and can incorporate different types of amino acids that the cell normally doesn’t like but it could be really important to incorporate so as to provide new functionalities to these proteins that we cannot currently make.
2.6 Do it-yourself biology: Amateurs becomes interested to understand biology and make instruments that could be used in organized groups to try and understand a biological phenomenon (Chuang et al., 2010).
3. Potential applications in synthetic biology
There are several different applications for synthetic biology. Researchers can use synthetic biology to figure out how to optimize organisms for specific applications, they can speed up their research so that they don’t have to do routine proteomics and genomics research. For example, one can make an antibody through synthetic biology that has a higher level of expression. There is a lot of hope that synthetic biology will be able to help produce new things that will be useful to human health, animals, pharmaceuticals, gene or cell therapy, tissue engineering, probiotics, diagnostics and so (Mukherji and Van Oudenaarden, 2009). Another area of importance is agriculture biology where we are trying to improve plants that are resistant to diseases, plants that are resistant to droughts, and give better feedstocks, in industries like generating bioenergy, and biofuels (synthetic biology helps in producing such animals which can contribute in generation of biofuels and bioenergy at higher efficiency), production of bulk chemicals (this is very important as one day we might run out of all of them and need an alternative way for the production of chemicals that we need daily). Synthetic biology has potential applications in the environment like biosensors, bioremediation, bioreporters, and waste treatment that may be helped by producing specific organisms to achieve what we cannot in normal conditions (Chuang et al., 2010) (Tripathi et al., 2018).
4. Bio-reporters for the environment Bio reporters are intact living microbial cells that have been genetically engineered to produce a measurable signal in response to a specific chemical or physical agent in their environment. Bio reporters contain two essential genetic elements: a promoter gene and a reporter gene. The promoter gene is transcribed when the target agent is present in the cell's environment. The promoter gene in a normal bacterial cell is linked to other genes that are there likewise transcribed and then translated into proteins that help the cell in either competing or adapting to the agent to which it has been exposed. In the case of a bio reporter, these genes have been removed or replaced with a reporter gene. Consequently, turning on the promoter gene now causes the reporter gene to be turned on. Activation of the reporter gene leads to the production of a reporter protein that automatically generates one type of detectable signal. Therefore, the presence of a signal indicates that a bio reporter has sensed a particular target agent in its environment. The Bio reporters are very simple engineered bacterial cells that are not pathogenic in the lab. These cells have small circuits inside which will recognise the compound that will diffuse inside the cell. The compound will bind to the sensory proteins present in the cell. This sensory protein can bind to DNA and direct the synthesis of a new protein in the cell, and the new protein made is such that it will give light or fluoresce (Fig.2). These bacterial cells are very simple and helps us in making analytical devices to sort of interrogating the part of an environment where we think there is contamination (for example arsenic contamination) (Ellis et al., 2011). <Fig. 2> 5. Future prospects of synthetic biology: building life to understand it Synthetic biology is a relatively new interdisciplinary field of science and the major areas for future research include: 5.1 Industrialization and automation Lots of research groups are working on synthetic cells but the real progress is probably happening at companies that automate the design, build test, learn cycle and particularly focus on strain optimization for stains that make molecules metabolically engineered (Erickson et al., 2011). 5.2 Machine learning for DNA design There is a huge opportunity for machine learning in synthetic biology because fundamentally DNA is the code that is written in a language like certain strings of letters and is understood by cells in certain orders and contexts to mean things and direct the cells to do stuff. Yet there is no full understanding of this language and what this code is because its learning has started in the last 70-80 years in molecular biology and biology (Flores Bueso and Tangney, 2017). 5.3 Synthetic cell mimics from biochemistry Synthetic cells from biochemistry are a big area for research. There are multiple communities that are partly in synthetic biology and sometimes just a bit more adjacent to synthetic biology, looking to put together biochemical reactions into things like liposomes and vesicles and try to build a cell and that is the nature of the US community, or make a synthetic cell which is more the name of the sort of European community. It may be possible to put a whole load of components into a vesicle and start to actually perform like life and then maybe we can stick DNA programs into it and they can become self-sustaining (El Karoui et al., 2019). 5.4 Cellular communities and multi-cellularity Building cells from scratch is the ultimate gain of function research because we are taking something that’s not living and making it live. A better understanding of the entirely new dimension where complexity and functionality include multiple different cells that do different tasks and have themselves arranged into multicellular systems. 5.5 Designing with whole cell simulations The current era is of whole-cell simulations. Presently many young bioinformaticians are working on the algorithms for designing the same. There is a whole-cell simulation of a cell cycle for M. genitalia and for E. coli and human cells in progress. Computational biologists study the intricate network of genetic circuits, and biological circuits and studies and information that we get from computational biology studies can actually inform the way we build cells. 5.6 Engineered organism for sustainability goals United Nations have multiple different sustainability goals and it is pretty hard to find any of those goals that don’t involve biology because there are things to do with healthcare, water purity, and scarcity of resources and so all these things link in with biology and the younger generation are growing up knowing there is going to be scarcity and it’s going to get worse for their lifetimes (Gardner et al., 2000). Synthetic biology encompasses any way of manipulating biological systems and systems biology defines those systems and helps us understand what should we work on. Synthetic biology is driving a manufacturing revolution that explores alternative feedstock and production processes and further extends towards the development of products of better performance. The above improvements are only the start. As the information on Synthetic Biology proceeds to progress, so does the innovation that goes with it. The control of DNA marks extraordinary significance inside the field. As referenced previously, it can give qualities to things that don't as of now have enough or every last bit of it (Lu et al., 2009). In any case, the most encouraging progression must be the improvement of "Synthia". Because of this advancement, DNA can be built from scratch. Things that can't be transferred can be constructed. This is a colossal progression since it can change our reality totally. The making of the new semi-synthetic living being is most certainly engaging and an accommodating advancement (Isaacs et al., 2004). 6. Advantages and disadvantages Synthetic Biology has the inclination to reform various fields including medication and energy creation. Researchers could utilize it to recognize and eliminate impurities from the air and water which could destroy various medical issues. Less fortunate nations could profit from headways of Synthetic Biology by having fresher water to drink and food with additional protein (MacDonald et al., 2011). Synthetic Biology can likewise contribute to the cultivating business by adjusting harvests to become quicker and better. It could likewise be the justification for building-coordinated agribusiness to work! Manufactured science applications could likewise be applied to analyse and screen infections in people and creatures and foster new medications and antibodies that sound more successful. Moreover, since Cancer is an illness that happens inside the cells of our body, it is conceivable that a cure for it exists in Synthetic Biology (Khalil and Collins, 2010). Synthetic Biology can likewise be applied to track down options to fuel, for example, the bio-fuels. Since everything revolves around controlling/making DNA, a little 'slip of a hand' or blunder can make immense things. The apprehension about having an end time or an existence where robots rule the world could transform into reality through Synthetic Science (Lu et al., 2009). Aside from this, there are different ventures that could appear to be wonderful with Synthetic Biology yet in all actuality can really hurt. An illustration of this is 'Resuscitate and Restore'. This includes resurrecting terminated species. Having the most extraordinary and wiped out species alive again sounds commendable anyway it very well may be unsafe from numerous viewpoints. Synthetic Science is additionally supposed to be off-base since it tends to be utilized in exceptionally hurtful ways. This incorporates making medications, and weapons and developing microorganisms that are deadly to people (Parul et al., 2021) (Smolke, 2009). 7. Conclusion Synthetic biology works with a bottom-up construction not dissection and instruction of organisms but taking parts and building something again. The move from portraying science to taking advantage of it for our necessities has forever been a piece of the organic endeavour and in this way continuously mirrored the flow of primary lines of natural examination. Thus, as sub-atomic science has for quite a while endeavoured to disentangle the atomic components that are significant in cell work, biotechnology has taken advantage of this information and embraced some of these instruments to create synthetic substances, chemicals and biopharmaceuticals. Presently, manufactured science is taking on an extremely aggressive plan in building novel organic substances on a perpetually perplexing level for novel applications. 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<surname>Johri*</surname>
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<abstract>
<p>Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Synthetic Biology is a science dealing with designing new biological devices and systems and also redesigning the existing natural biological system as green technologies that can act as alternatives for various chemical and petroleum industries. It is an interdisciplinary area that basically utilizes engineering principles to modify the existing organisms or altogether make a novel one for conventional biological research. Synthetic biology is a multidisciplinary zone of exploration that seeks to construct new biological fragments, devices, and systems, or to reshape systems that are at present found in nature. This new branch of science has contributed significantly to human health, the environment, basic life science and pharmaceutical science and many more. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. Synthetic biology technologies are budding, fetching the way that almost everything can be contrived sustainably and competitively. Industries must learn to utilize syn-bio to grow new products and methods, improve on the existing ones, and lessen the costs to remain viable in the upcoming times. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.
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<kwd> Bioreporters</kwd>
<kwd> Biosensors</kwd>
<kwd> Synthetic cell</kwd>
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