Revolutionary Genetic Code Discovery in Archaea Unlocks Bioengineering Potential

Scientists from the Department of Energy's Oak Ridge National Laboratory (ORNL) and the Innovative Genomics Institute (IGI) at the University of California, Berkeley, have identified a unique genetic code within certain microbes known as Archaea. This discovery expands the known cellular building blocks in living organisms. New insights into microbial genetics and bioengineering pathways may lead to innovations in fuels, chemicals, materials, and drug therapies, while also aiming to advance U.S. competitiveness in the biotechnology sector.

New insights into microbial genetics and bioengineering pathways may lead to innovations in fuels, chemicals, materials, and drug therapies, while advancing U.S. competitiveness in biotechnology.

Discovery Details

In most organisms, a DNA sequence of TAG acts as a stop codon, signaling the termination of amino acid sequences during protein construction. However, the research team found that some Archaea have developed the capability to reinterpret this signal. Instead of stopping, they incorporate pyrrolysine (Pyl), a rare amino acid, into their proteins.

This mechanism allows cells to customize protein functions and may contribute to the microbes' ability to survive in extreme environments. Prior to this finding, alternative genetic codes were not known for Archaea.

Experimental Confirmation

ORNL's Bioanalytical Mass Spectrometry Group confirmed the consistent integration of Pyl into Archaea proteins where TAG codons were present. This was achieved by analyzing hundreds of proteins simultaneously, indicating a widespread incorporation across the cells' proteomes.

Researchers further confirmed Pyl incorporation in two Archaea strains previously hypothesized to use it based on metabolic genes. The genetic machinery responsible for Pyl incorporation was successfully transplanted into E. coli, demonstrating its function in a different organism commonly used in biotechnology.

Implications

This finding suggests that the genetic code is not static and can evolve naturally. The discovery creates a novel pathway for bioengineering, potentially leading to:

• Custom Microbes: Development of microbes tolerant to industrial processes for producing new fuels, chemicals, and materials.
• Enhanced Drug Therapies: Engineering proteins for medicines that could bind more precisely to target cells, such as cancer cells, and exhibit increased longevity in the body with reduced side effects.
• Improved Plant Microbiomes: Boosting the performance of bioenergy crops.