18-Feb-2020 - Max-Planck-Institut für Biochemie

Biological machine produces its own building blocks

Researchers have for the first time developed a genome the size of a minimal cell that can copy itself

The field of synthetic biology does not only observe and describe processes of life but also mimics them. A key characteristic of life is the ability to ability for replication, which means the maintenance of a chemical system. Scientists at the Max Planck Institute of Biochemistry in Martinsried generated a system, which is able to regenerate parts of its own DNA and protein building blocks.

In the field of synthetic biology, researchers investigate so-called “bottom-up” processes, which means the generation of life mimicking systems from inanimate building blocks. One of the most fundamental characteristics of all living organism is the ability to conserve and reproduce itself as distinct entities. However, the artificial “bottom-up” approach to create a system, which is able to replicate itself, is a great experimental challenge. For the first time, scientists have succeeded in overcoming this hurdle and synthesizing such a system.

A biological machine produces its own building blocks

Hannes Mutschler, head of the research group "Biomimetic Systems" at the MPI for Biochemistry, and his team are dedicated to imitate the replication of genomes and protein synthesis with a “bottom-up” approach. Both processes are fundamental for the self-preservation and reproduction of biological systems. The researchers now succeeded in producing an in vitro system, in which both processes could take place simultaneously. "Our system is able to regenerate a significant proportion of its molecular components itself," explains Mutschler. In order to start this process, the researchers needed a construction manual as well as various molecular "machines" and nutrients. Translated into biological terms, this means the construction manual is DNA, which contains the information to produce proteins. Proteins are often referred to as "molecular machines" because they often act as catalysts, which accelerate biochemical reactions in organisms. The basic building blocks of DNA are the so-called nucleotides. Proteins are made of amino acids.

Modular structure of the construction manual

Specifically, the researchers have optimized an in vitro expression system that synthesizes proteins based on a DNA blueprint. Due to several improvements, the in vitro expression system is now able to synthesize proteins, known as DNA polymerases, very efficiently. These DNA polymerases then replicate the DNA using nucleotides. Kai Libicher, first author of the study, explains: "Unlike previous studies, our system is able to read and copy comparatively long DNA genomes.” The scientists assembled the artificial genomes from up to 11 ring-shaped pieces of DNA. This modular structure enables them to insert or remove certain DNA segments easily. The largest modular genome reproduced by the researchers in the study consists of more than 116,000 base pairs, reaching the genome length of very simply cells.

Regeneration of proteins

Apart from encoding polymerases that are important for DNA replication, the artificial genome contains blueprints for further proteins, such as 30 translation factors originating from the bacterium Escherischia coli. Translation factors are important for the translation of the DNA blueprint into the respective proteins. Thus, they are essential for self-replicating systems, which imitate biochemical processes. In order to show that the new in vitro expression system is not only able to reproduce DNA, but is also able to produce its own translation factors, the researchers used mass spectrometry. With this analytic method, they determined the amount of proteins produced by the system. Surprisingly, some of the translation factors were even present in larger quantities after the reaction than added before. According to the researchers, this is an important step towards a continuously self-replicating system that mimics biological processes.

In the future, the scientists want to extend the artificial genome with additional DNA segments. In cooperation with colleagues from the research network MaxSynBio, they want produce an enveloped system that is able to remain viable by adding nutrients and disposing of waste products. Such a minimal cell could then be used, for example, in biotechnology as a tailor-made production machine for natural substances or as a platform for building even more complex life-like systems.

Facts, background information, dossiers

  • synthetic biology
  • genomes

More about MPI für Biochemie

  • News

    New method revolutionizes cancer diagnosis

    How does cancer arise? How does cellular composition influence tumor malignancy? These questions are profound and challenging to answer, but are crucial to understand the disease and find the right cure. Now, a German-Danish team led by Professor Matthias Mann has developed a ground-breakin ... more

    MaxDIA – taking proteomics to the next level

    Proteomics produces enormous amounts of data, which can be very complex to analyze and interpret. The free software platform MaxQuant has proven to be invaluable for data analysis of shotgun proteomics over the past decade. Now, Jürgen Cox, group leader at the Max Planck Institute of Bioche ... more

    In the right place at the right time

    Proteins are molecular work horses in the cell that perform specific tasks, but it is essential that the timing of protein activities is exquisitely controlled. When proteins have fulfilled their tasks, degradation of these proteins will end processes that are unneeded or detrimental. To co ... more

More about Max-Planck-Gesellschaft

  • News

    Pumping up the music of molecules

    Sensitive animal noses can sniff out trace particles, such as volatile organic compounds, in the ambient air. Humans, on the other hand, are developing innovative technologies for this purpose, such as optical spectroscopy. This uses laser light to detect the molecular composition of gases. ... more

    How to find marker genes in cell clusters

    The thousands of cells in a biological sample are all different and can be analyzed individually, cell by cell. Based on their gene activity, they can be sorted into clusters. But which genes are particularly characteristic of a given cluster, i.e. what are its “marker genes”? A new statist ... more

    Cell-culture breakthrough: Advanced “mini brains” in the dish

    “Outer Radial Glia” (oRG) cells are nervous system stem cells that are instrumental for the development of the human cortex and have been challenging to produce in the lab. Now, a team of Max Planck researchers from Berlin succeeded in generating brain organoids that are enriched with these ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: