Synthetic Biology and Artificial Genetic Systems in the Lab

From an engineer’s point of view, biology has a frustrating lack of standardized parts. Usually, a microprocessor designed in drafted software is produced and functions exactly the way it’s supposed to once it has been stamped, fabbed and machined. The goal of Synthetic Biology is to be able to provide solutions to problems in the same way an electronic circuit can be engineered.

Eric Matthews Eric Matthews

Biology is a nearly endless series of nano-machines and the nano-assemblers that make them. Making biology more of a technology--more like software that runs in a cell instead of on a silicon chip--opens up many possibilities. Researchers and product developers would have the ability to work with a simplified, standardized version of biochemistry that could be written like computer code, or snapped together like Legos. The tools of synthetic biology can permit orders to be executed in a way that someone with access to the programming language of the cell could productively use synthetic biology without having to understand all of the natural biology.

Fig. 1: Overview of X-SELEX. Source:

Old designs, new processes

About 1040 organisms have lived on Earth in the last 4 billion years. In that time, they have had chances to stumble across many elegant solutions to the challenges faced by those cells. The path to those solutions, though elegant in the end, often looks like a random, stumbling walk. An electrical engineer may consider dealing with all this randomness and evolution and fluid to be fool’s errand. Being accustomed to such errands, molecular biologists are making tremendous progress towards reducing systems to a collection of standardized components. Synthetic biologists look for evolved solutions that already exist in nature, then try to adapt them to solve new problems. Synthetic biology is being used to create drugs, store and process data, treat cancer, make food, deliver targeted medical treatments and create whole new forms of life that don’t share our basic biochemistry. There is no immediate cause for alarm.

Protein design and re-design

Some of the most interesting new synthetic biology advances involve the standardization of biological parts by introducing codons that code for non-typical amino acids or creating DNA replication apparatus that utilize base pairs different from the naturally occuring C, T, A and G. By using the tools and machinery of standard biology but re-designing them to expand the potential set of functions and processes, two advantages are conferred. First, the standardization of the system makes future processes easier to plan, and hopefully, execute. Second, by using nucleic acids and amino acids that aren’t present in typical Earth biochemistry, that biochemistry can exist without running afoul of the regulation mechanisms that exist natively within a cell. 

Expanding the set of possible protein functions

Using chemical structures that function like our biology- but that life doesn’t currently use- opens the possibility of creating aptamers that bind to specific targets in a cell, but are resistant to degradation. It may possible to create enzymes (XNAzymes) that target a protein involved in a disease process without running afoul of the typical inhibitory pathways that regulate naturally occurring enzymes. Eventually, synthetic biologic gene therapies expressing enzymes within a cell may be able to target and cleave mRNA involved in oncogenic pathways, killing cancer cells discriminately from within. Similarly, engineered, natively expressed enzymes can cleave bacterial or viral RNA in a way that it would be difficult for pathogens to evolve a resistance to. 

Natural product synthesis

Outside of medical treatments, there are numberless potential synthetic biology applications that can be exploited right now for use in consumer products. The heme in plant-based, meat replacements is produced by synthetic biology, contributing a meaty flavor and color to food without resorting to any activity that a cow would find threatening. A synthetic biologic anti-malarial drug, artimisinin is being produced by the company Amyris, instead of being extracted from the Artemisia annua plant. Being able to produce the compound from yeast in a controlled environment, means the supply is increased and production has become more stable. In the future, cell-free systems--the molecular machinery of cells--can be used to produce compounds of interest while dispensing with the burdensome requirement of actually needing to keep cells alive. Likewise, such approaches can be employed to generate novel protein variants as highlighted in the application note: Cell-free extract protein synthesis: Rapid single vessel DNA assembly and protein production in microliter scale.

Fig. 2: Schematic of DAG sensor.


Completing a circuit

Biosensors are one of the earliest uses of modern synthetic biology. Introducing a novel biological circuit into a cell--most typically a bacteria--with one component responsible for detecting an event or the presence of a compound of interest, and another component that indicates a response. Soil bacteria can be engineered to include a biosensor that luminesces when it is in an environment that is contaminated with heavy metals. Montana Molecular is a company that produces genetically encoded biosensors that can be introduced into mammalian cells. Biosensors working in live cells confer several advantages that non synthetic biological methods may not. Measurement is rapid and continuous. Specificity of detection is as high. Special reagents and wash steps may not be needed for detection and the response time for detection may be as fast as the time it takes for a molecule to enter a cell.

Read the application note here:

AN301: Simultaneous detection of GPCR second messengers in living cells

Intracellular biosensors are some of the synthetic biology techniques most readily suited to be used in a microplate format. Detecting the activity of G-protein coupled receptors is always going to be useful in the lab. But right now, BMG Labtech’s customers are already using synthetic biology tools related to rapid gene synthesis, synthetic transcription factors and tunable protein:protein interactions. It’s only a matter of time before these techniques and components are part of every life scientist’s toolkit.





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