Wednesday 13 April 2022

Bacteria - optogenetic reprogramming

Researchers have found that engineering the light-dependent proton pump rhodopsin into Escherichia coli redirects carbon flow from cellular metabolism to biosynthetic product generation. This approach of using light as an energy source can help improve the efficiency of target compound production and reduce CO2 emissions.

 

Researchers have revealed that microorganisms can be engineered to use light for energy, freeing up cellular resources to produce biomanufactured products.

 

Metabolically engineered microorganisms are used to produce various useful chemicals throughout the world, but there's a catch: both microbial growth and chemical synthesis require a molecule called ATP as an energy source. Because of this, keeping the cellular "factories" healthy limits chemical production.

 

The researchers reasoned that instead they could use light, an external energy source, to improve production of useful substances without disrupting the microorganisms' natural metabolism.

 

To test this, the researchers introduced a heterologous membrane protein called rhodopsin into Escherichia coli, a common microorganism used in biomanufacturing. Rhodopsin is a pump that is activated by light, and the action of the pump leads to the generation of ATP without using the cell's natural machinery (known as the TCA cycle and respiratory chain) to produce it. This approach has the added benefit of reducing the emission of carbon dioxide, a byproduct of the TCA cycle.

 


 

The cells expressing rhodopsin generated significantly more chemical products when exposed to light, and the carbon flow in these cells was directed away from energy generation and toward chemical synthesis.

 

Once they had proved that this concept worked for various compounds such as 3-hydroxypropionate, mevalonate, and glutathione, the researchers went on to create three new strains of E. coli. One of these strains expressed super-rhodopsins with even better pump activities than the original rhodopsin that was tested.

 

The other two strains incorporated synthetic biological systems that provided an intrinsic supply of retinal, the activator of rhodopsin, and optimized the balanced expression of multiple genes in the relevant metabolic pathway.

 

The findings suggest that biomanufactured microorganisms designed to use light for energy source can be used to efficiently biosynthesize useful target compounds.

 

This new approach is expected to increase the efficiency of producing useful materials through fermentation and other bioprocesses while simultaneously reducing carbon emissions.

 

See:

 

Yoshihiro Toya, et al.  Optogenetic reprogramming of carbon metabolism using light-powering microbial proton pump systems. Metabolic Engineering, 2022; 72: 227 DOI: 10.1016/j.ymben.2022.03.012

 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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