Improved Biomanufacturing Using Biological Clock Control for High Yield/Low Cost Bioproduct


Summary

A team of researchers at Vanderbilt University has developed a method of manipulating the circadian clock of cyanobacteria. This biological manipulation is used to increase gene expression in target genes that produce biofuel and high-value bioproducts, such as pharmaceuticals and cosmetics from precursor-expressing genes. Altering the circadian rhythm in the bacteria provides an improved approach to bioproduct development on a large scale using sunlight as a zero–cost energy solution.

Addressed Need

Rising industry interest in bioproducts like biopharmaceuticals and cosmetics has prompted the need for low cost but large output methods to create these products. There are few methods currently available to produce large amounts of bioproducts from bacterial sources that do not involve using expensive medium as energy. Photosynthetic organisms that get their energy from light is a perfect solution. However, very few tools exist to alter the metabolic capabilities of photosynthetic microbes that would prompt increased gene expression in the pathways associated with bioproduct formation.

Technology Description

The current challenges associated with rhythmic gene expression are the limitations in the amount of bioproduct that can be produced, and when it can be produced. In order to combat these challenges, the researchers targeted the biological clock that regulates the daily ‘awake’ and ‘asleep’ phases of the bacteria, which follow day and night. In order to maximize the amount of bioproducts produced, the biological clock of the bacteria was inactivated while in an active or awake phase so that the organism thinks that it is daytime all the time. This was accomplished by reprogramming the circadian rhythm of the bacterial organisms so that gene expression is constant instead of periodic, allowing the expression to continue in a state of constant activation when exposed to continuous illumination.

To maximize the product output of the organisms in this state, the organisms also had to be altered so that the maximum level of gene expression for the intended output was the new constant organism state. By placing the organism in a constant state of maximum gene expression, more of the intended bioproduct would be produced consistently. 

Fig. 1 Improvements in gene expression that result from biological clock control.

Unique Properties and Applications

•       This method of gene expression control can be applied to many different production targets, such as biofuels, biopharmaceuticals (insulin), and cosmetics

•       Manipulating biological processes improves the output of target genes due to continuous expression

•       Bioproduct production is increased creating a lower cost method based on light as the energy input rather than expensive media

Technology Development Status

Researchers have performed extensive testing to optimize the manipulation of bacterial processes in lab settings.

Intellectual Property Status

US Patent Application Pending

 


Licensing Contact

Masood Machingal

615.343.3548