Synthetic Biology Parts, Devices and Applications

(Nandana) #1
49

Synthetic Biology: Parts, Devices and Applications, First Edition. Edited by Christina Smolke.
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA.


4


Engineered biological parts, devices, and systems come to life when grafted into
a living cell. Host cells are organisms shaped by billions of years of evolution and
characterized by high complexity, robustness, and the ability to adapt and evolve
in response to fluctuations in their natural environment. For synthetic biological
applications, where precise engineering of biological systems with predictable
outputs is attempted, host cells displaying reduced complexity, higher genetic
stability, and increased efficiency are desired. We show here that streamlining,
the elimination of genomic regions unnecessary or counterproductive in bio-
technological applications, is a promising way to produce host cells, which can
outperform their natural ancestors in the less fluctuating environment of labora-
tory settings. We focus here on the streamlining of E. coli, a primary host cell in
research and industry. The rationale behind the streamlining process, identifica-
tion of genomic parts targeted for elimination, deletion techniques, and results
and applications of genome reduction projects will be presented. Current chal-
lenges, obstacles, and possible future directions of genome streamlining will also
be discussed.


4.1 Introduction


Synthetic biological constructs – genetic circuits, modules, and devices – usually
work in the context of a living cell. The information coded in the artificial blue-
print, and embedded in the host genome, must be maintained and expressed by
the cellular machinery of information processing. Ideally, the new construct
functions in a predictable way and uses the cellular resources without much
interference with the basic physiology of the host.
Natural host cells, even relatively simple bacteria, however, provide an
extremely complex and frequently unpredictable environment for the synthetic
construct, causing interference with the desired function [1, 2]. Moreover, since


4 Rational Efforts to Streamline the Escherichia coli Genome


Genome


Gabriella Balikó, Viktor Vernyik, Ildikó Karcagi, Zsuzsanna Györfy,
Gábor Draskovits, Tamás Fehér, and György Pósfai


Biological Research Centre of the Hungarian Academy of Sciences, Institute of Biochemistry, Synthetic and Systems
Biology Unit, Temesvari krt. 62, Szeged, 6726, Hungary

Free download pdf