Thursday, 6 June 2019

Creating ‘smart’ microbial bionsensors

New research shows that protein-based biosensors can detect the presence of a desired enzyme target and respond by physically lighting up, and enabling researchers to immediately identify cells with increased overall enzyme yield.

The implications of this smart microbial cell concept are to offer an advanced platform for high throughput screening for enzyme discovery, design, and evolution. The approach, which comes from Los Alamos National Laboratory, can be translated to screening of metagenomic samples, rational enzyme design, or directed evolution of known enzymes. The technology is adaptable to a single enzyme, or a pathway, or global optimization of an industrial strain.

To discover more, I spoke with researcher Ramesh Jha.

Tim Sandle: How important are biofuels in terms of addressing energy demand?

Ramesh Jha: Biofuels and commodity chemicals made from renewable biomass using enzymes or microbes are considered sustainable routes and their use circumvents dependency on fossil fuels. Added to that, fuels and commodity chemicals come with a high carbon footprint while biofuels and biocommodities from renewable sources is an efficient recycling of carbon and leave a low carbon footprint.

Tim Sandle: What are the different types of biofuels and how do they differ in terms of production?

Jha: Various biofuels, biocommodities and bioplastics can be ‘drop in’ or ‘functional replacements’ of the existing fuels, commodity chemicals or polymers mostly derived from petroleum sources.

Tim Sandle: How did you develop your protein-based biosensors?

Jha: Our protein-based biosensors are inspired by nature, where a class of proteins called transcription factors (TF) gets activated in the presence of a molecule and regulate the production of other proteins for function (OPF) . If TF is engineered to interact with an enzymatic product and the OPF is a fluorescent protein reporter, then the enzymatic activity in a microbial cell can be correlated to the fluorescence response in the cell.

Tim Sandle: How do the biosensors identify the desired enzyme target?

Jha: Enzymatic activity results in a chemical product. This product activates the biosensor, which responds by producing and accumulating a fluorescence "reporter." The enzymatic activity is visualized by the presence of light.

Tim Sandle: What are the practical benefits of this identification?

Jha: What we see, we believe. Cellular fluorescence due to the enzymatic activity can be easily visualized using a flow cytometer with ultra high throughput and sensitivity. Measuring the product in a cell is otherwise a tedious and slow step.


A biofuel is a fuel that is produced through biological processes (such as agriculture) as opposed to geological processes (like fossil fuels). Renewable biofuels either involve carbon fixation, such as those that occur in plants or microalgae through the process of photosynthesis; or, they are created by the conversion of plant material.

Tim Sandle: Has industry shown an interest in this development, in relation to biofuels?

Jha: Industries are interested in testing millions of variants of microbial strains or enzymes. Since the biosensor technology can be easily adapted for high-throughput screening, industries are getting interested in this technology.

Tim Sandle: Are there any other practical applications for this technology?

Jha: This technology can be applied to optimization of enzymes or microbial strains with applications in biomanufacturing as well as medical therapeutics and environmental clean-up.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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