Cells of higher organisms use cell organelles to
separate metabolic processes from each other. This is how cell respiration
takes place in the mitochondria, the cell's power plants. They can be compared
to sealed laboratory rooms in the large factory of the cell. A research team at
51猎奇 has now succeeded in creating artificial cell organelles and
using them for their own devised biochemical reactions.
FRANKFURT. Biotechnologists
have been attempting to 鈥渞eprogram" natural cell organelles for other processes
for some time 鈥� with mixed results, since the 鈥渓aboratory equipment" is
specialised on the function of organelles. Dr Joanna Tripp, early career
researcher at the Institute for Molecular Biosciences has now developed a new
method to produce artificial organelles in living yeast cells (ACS Synthetic
Biology: ).
To this end, she used the ramified system
of tubes and bubbles in the endoplasmic reticulum (ER) that surrounds the
nucleus. Cells continually tie off
bubbles, or vesicles, from this membrane system in order to transport substances
to the cell membrane. In plants, these vesicles may also be used for the
storage of proteins in seeds. These storage proteins are equipped with an
鈥渁ddress label" 鈥� the Zera sequence 鈥� which guides them to the ER and which
ensures that storage proteins are 鈥減ackaged" there in the vesicle. Joanna Tripp
has now used the 鈥渁ddress label" Zera to produce targeted vesicles in yeast
cells and introduce several enzymes of a biochemical metabolic pathway.
This represents a milestone from a
biotechnical perspective. Yeast cells, the 鈥減ets" of synthetic biology not only
produce numerous useful natural substances, but can also be genetically changed
to produce industrially interesting molecules on a grand scale, such as
biofuels or anti-malaria medicine.
In addition to the desired products,
however, undesirable by-products or toxic intermediates often occur as well. Furthermore,
the product can be lost due to leaks in the cell, or reactions can be too slow.
Synthetic cell organelles offer remedies, with only the desired enzymes (with
鈥渁ddress labels") encountering each other, so that they work together more
effectively without disrupting the rest of the cell, or being disrupted
themselves.
鈥淲e used the Zera sequence to introduce a
three-stage, synthetic metabolic pathway into vesicles," Joanna Tripp explains.
鈥淲e have thus created a reaction space containing exactly what we want. We were
able to demonstrate that the metabolic pathway in the vesicles functions in
isolation to the rest of the cell."
The biotechnologist selected an industrially
relevant molecule for this process: muconic acid, which is further processed industrially
to adipic acid. This is an intermediate for nylon and other synthetic
materials. Muconic acid is currently won from raw oil. A future large-scale
production using yeast cells would be significantly more environment-friendly
and sustainable. Although a portion of the intermediate protocatechuic acid is
lost because the vesicle membrane is porous, Joanna Tripp views this as a
solvable problem.
Professor Eckhard Boles, Head of the
Department of Physiology and Genetics of Lower Eukaryotes observes: 鈥淭his is a
revolutionary new method of synthetic biology. With the novel artificial
organelles, we now have the option of generating various processes in the cell anew,
or to optimise them." The method is not limited to yeast cells, but can be
utilised for eukaryotic cells in general. It can also be applied to other
issues, e.g. for reactions that have previously not been able to take place in
living cells because they may require enzymes that would disrupt the cell
metabolic process.
Publication:
Mara Reifenrath, Mislav Oreb, Eckhard
Boles, Joanna Tripp: Artificial
ER-Derived Vesicles as Synthetic Organelles for in Vivo Compartmentalization of
Biochemical Pathways, in:
ACS Synthetic Biology:
Further
information:
Dr. Joanna Tripp
Institute for Molecular Biosciences
51猎奇 Frankfurt
Tel.:
+ 49 69 798 29516
j.tripp@bio.uni-frankfurt.de
