Enzymes, which are biological nanomachines, play a crucial role in life’s chemistry by facilitating necessary reactions. Due to their versatility and power, enzymes have significant potential in biotechnology. They can be used to synthesize or modify pharmaceuticals and break down pollutants. However, the vast majority of bacteria, which contain genes encoding a wide range of enzymes, remain unstudied because they cannot be grown in laboratory conditions.
To address this issue, our team has treated the entire bacterial DNA found in soil as “genetic software.” We transfer this software to laboratory bacterial strains and screen for desirable new functions and isolate the responsible enzymes. This approach allows us to tap into the untapped potential of bacteria and discover new enzymes.
Traditional culturing methods used to collect soil samples and culture bacteria have limitations, as they miss out on the majority of bacterial species present. DNA-sequencing technologies have revealed that a gram of soil contains thousands of microbial species, many of which are difficult to grow. These hard-to-grow bacteria often possess genes with unknown functions, some of which can help solve major problems.
Genes are like units of information within living cells, and when activated, they produce proteins, most of which are enzymes. Enzymes act as catalysts for the chemistry that occurs in cells. While an enzyme may have a primary function that contributes to a cell’s well-being, it can also have multiple minor functions that may or may not be valuable. These minor roles are important for evolution as they may become essential when new stresses arise.
Our team aims to leverage the evolutionary potential of unknown enzymes from soil-dwelling bacteria to address important problems. We collaborate with Te Herenga Waka’s Living P? team to discover new enzymes from soil samples collected with their permission.
Enzymes can also be used to tackle problems such as bacterial resistance to antibiotics. Bacteria often possess enzymes that provide low levels of protection against new antibiotics, leading to the evolution of antibiotic resistance. Understanding how bacterial resistance arises allows us to develop countermeasures in a timely manner.
Additionally, we are interested in how unknown enzymes encoded by unknown genes can be directly useful or evolve to be useful in applications that protect and preserve the environment. For example, enzymes can aid in plastic recycling or remediation of environmental pollutants.
Our latest work represents a breakthrough in studying the millions of unknown genes present in soil samples. We extract all bacterial DNA from soil, break it into smaller fragments containing one or two genes, and introduce them into a laboratory bacterium called Escherichia coli. Our innovative approach lies in accessing the information within these newly introduced genes, which is challenging due to compatibility issues. However, we have developed a universally applicable emulator that allows E. coli to run most of the new software.
By screening individual E. coli bacteria with new properties of interest, such as pollutant degradation, we can identify enzymes that may initially be inefficient but can be improved through mimicking natural evolutionary processes in the lab.
Enzymes offer safe and controlled solutions to various problems as they are non-living, biodegradable, and incapable of replication. The key is finding enzymes that can effectively perform the desired tasks.