A protein from cyanobacteria has been redesigned into a homing beacon to attract molecular payloads. The long-term goal: to organize resources inside living cells for medical or industrial applications.
'Hoarding' resources in the same location encourages more efficient chemical reactions. Someday, we could use this system to enhance the production of rubber, biofuels, and other commodities.
The genetically engineered shell is based on natural structures and the principles of protein evolution. Scientists see such structures as a source of new industrial or medical technologies.
MSU scientists report how cyanobacteria line up their CO2-fixing factories within them in a system that works like Velcro. The research is part of an effort to control and repurpose these factories to make products for human consumption.
The new methods let scientists assemble the factories on demand and insert custom molecules inside them for further processing. The aim is to eventually design sustainable medical, industrial, or energy applications.
The Kerfeld lab announces two new methods for manipulating bacterial factories for biotech aims: one is to screen and extract the factories, the other is to predictably insert custom enzymes in them.
A peek into the logistics of how bacterial nanofactories move electrons, towards creating chemical products. Future apps include renewable energy and medical tools.
In a new Science publication, The Kerfeld lab show us the details of bacterial organelle shells for the first time ever, making it easier to target them for medical or renewable energy applications.
The Kerfeld lab has analyzed over 200 sets of cyanobacteria DNA. This knowledge is getting us closer to understanding how to build synthetic factories that will someday produce green fuels or products used to diagnose diseases.
The new compartment, widely spread among different kinds of bacteria, might be reassembled to someday sustainably produce “green” chemicals, medicines, and renewable energy.
Perspectives on building nanofactories for energy and medical uses
At the MSU-DOE Plant Research Laboratory (PRL), we are gathering scientists with varied areas of expertise to tackle key science problems through many angles – problems that are too large to address in single, isolated labs.
A major challenge, supported by the US Department of Energy's Office of Basic Energy Sciences, brings together 4 labs to understand, and, someday, build nanofactories, inspired by nature, to develop renewable energy sources addressing climate change or new chemicals for industrial or medical purposes.
Nanofactories in nature are found in many bacteria, and they have evolved to make a wide range of products, depending on the host’s needs. After all, bacteria that make these structures are highly diverse and found everywhere on the planet, from polar ice to scalding hot springs.
For example, one nanofactory produces energy out of carbon dioxide and sunlight in bacteria that live in waters like oceans and alpine lakes.
Another, in gut bacteria, isolates a toxic molecule, a smart trick that protects the host from poisoning itself, while helping it beat out other competing bacteria.
Special protein walls
What makes these nanofactories distinct, compared to normal cellular processes, is that they are protected by walls made of protein. This isolates them into small compartments inside the hosts (hence the ‘official’ name: bacterial microcompartments, or BMCs for short), which comes with some perks:
- The wall controls what raw material ( metabolites) comes in and what product comes out. This allows the cell to carefully control the reactions inside, with no unwanted interference.
- The wall concentrates all production in one space, like bringing all employees together on one car assembly line. That increases productivity and speed.
The PRL wants to eventually repurpose these nanofactories to make things they usually don’t in nature, like:
- Renewable materials, such as biofuels, plastic, or rubber, which currently come from trees and fossil fuels;
- Medical applications that neutralize harmful bacteria or target difficult diseases.
“We know that all these nanofactory walls are made of three flavors of proteins found throughout nature: BMC-H, BMC-T, BMC-P” according to Eric Young, a grad student in the Ducat lab. “They all fit together, like Lego bricks, and just like Legos, they can be used to build many different types of structures.”
“If we can figure out how these different proteins interact with each other, we would have a “Lego-like” assembly toolbox for making custom nanofactories and other types of assemblies. Then we can tailor what types of applications we use them for.”
Nanofactories in different shapes for more functions
Just recently, the Kerfeld lab revealed our first view of the compartment wall and how the three types of Lego bricks fit together (see below). Understanding how the pieces of the wall fit together will help us tinker with how to build custom structures.
But Eric and other members of the team are tackling this concept differently. Instead of studying all three proteins, they are looking into what would happen if the individual protein Lego bricks assembled by themselves, without the other flavors.
“This approach revolves around using individual proteins as a way to build different nanostructures inside of cells, as new assembly lines for diverse applications. They would look different from the main nanofactory compartment.”
In other words, the more options we have for building nanofactories, the more applications we can imagine.
Eric’s recent focus has been on the BMC-H brick.
“Originally, we thought all BMC-H Lego bricks would form these striking, large nanostructures when put together in a cell. This didn’t happen in the case of one type of BMC-H brick. These different BMC-H bricks assembled into some striking shapes, from tubes, rods, to even ‘Swiss rolls’ (think of a rolled-up carpet).”
This result is leading the team down a line of thinking that subtle differences in the bricks lead to changes in how they assemble. And something unique about each protein flavor leads to them forming different shapes.
Some of these subtle differences occur at the junctures where the individual bricks come together.
“For example, we used computer simulations, with help from Oak Ridge National Lab, to further investigate two of the BMC-H Lego bricks. Amazingly, the simulations suggest that the brick which assembled into tubes inside living cells, also preferred to associate at an angle in the simulations. This provides a clue as to why this particular BMC-H curls in on itself to form a tube when many of them are connected in a series.”
Eventually, the team hopes to codify what they like to call “design principles” – basically, a set of predictive rules for how the various Lego bricks like to assemble.
These principles would suggest how to accurately build new structures and design useful functions into them.
“For example, a tube shape could be used as a tiny pipeline inside the cells, allowing raw precursors to flow in and products—like biofuels or medicines—to flow out,” Eric says.
Or, he adds, structures like rods and sheets could be used as surfaces to program new function into the cells – think like little molecular switchboards!
“We have already made some good strides by realizing that subtle differences can change how the individual blocks assemble. Now, we are using knowledge of the structure of the protein to change properties of the blocks, in a “design, build, test, repeat” cycle, to tease out the rules of assembly.”
This work was primarily funded by the US Department of Energy, Office of Basic Energy Sciences. Eric’s paper is published in Frontiers in Microbiology under a special issue of “Novel Metabolic Engineering Approaches for Producing Novel Chemicals.”
The protein, peroxiredoxin Q, is known to maintain a healthy balance of chemicals and energy levels in chloroplasts. The new research shows the protein also impacts the system that produces chloroplast membranes.
The CAMTA system - which is known to protect plants from cold weather - plays a newly discovered role: when bacteria invade a leaf, CAMTA warns neighboring, unaffected leaves to prepare for invasion.
When algae get stressed, they hibernate and store energy in forms that we can use to make biofuels. Understanding how stress impacts algal hibernation could help scientists lower the cost of biofuels production.