Synthetic Biology | Definition and delimitation
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2.2.4
Is it synthetic biology or still conventional biotechnology?
Many approaches are in the interphase between conventional biotechnology practice and synthetic biology.
According to Nielsen and Keasling (2011) the difference may be described as a “platform cell factory” that
would not naturally produce any of the
chemicals, and into which a synthetic (rationally designed or synthetic)
pathway is transferred (synthetic biology). Montague et al. (2012) define and distinct synthetic genomics from
genetic engineering based on “engineering and manipulation of genetic material of an organism on the scale
of the whole genome either in terms of number of base-pairs, or number of loci engineered” as the major
feature. In addition, even if the scope is engineering an individual biosynthetic pathway, the “pathway must
function in a biochemical and regulatory context with many inputs and outputs” (Montague et al. 2012).
Key components for the construction of non-natural pathways are synthetic DNA, advanced molecular
switches for controlling the state of the metabolism, and protein and pathway engineering provided by
synthetic biology (Stephanopoulos 2012). By applying these components enzyme activity and specificity is
improved, cofactors and currency metabolites are balanced, yields are increased and effective direct product
synthesis is achieved. Although a pathway might be coded for by only a few genes, changes to the genome,
e.g. by increasing the yield, highlights the difference between synthetic biology and genetic engineering
(Montague et al. 2012).
2.3
Some limits to “bio-part engineering”
The understanding of biology will continue to be for a long time the limiting component in any attempt to
reconstruct or emulate biological systems, in whole or in part (Stephanopoulos 2012). Understanding the
context of metabolic networks and its correlation with metabolite concentrations is one of the major
challenges to which meta-omics studies contribute significantly (Boyle and Silver 2012). However, the
complexity of living cells to date surpasses the complexity of human-made devices. Due to limited background
knowledge complete forward engineering of entire cells is not yet possible (Nielsen and Keasling 2011). In the
long term plant metabolism could be engineered based on synthetic strategies to produce compounds with
novel chemical properties (Zurbriggen et al. 2012). However, to date the engineering of biosynthesis pathways
is tedious due to its complexity and consequently limited knowledge, in particular on plant genes. Successfully
assembled biological systems are still of low actual complexity and typically contain less than ten promoters
(Purnick and Weiss 2009) or have limited capacity concerning assembly of genes and their maximum size (Xu
et al. 2012). Furthermore, important synthetic biology tools are currently only demonstrated within
Escherichia coli and
Saccharomyces cerevisiae, limiting these tools to a narrow set of organisms (Montague et
al. 2012). Most projects are being realised in laboratory cultures of microorganisms.
The result of the engineering process when aiming at the production of desirable compounds has to be high
yield and high titres (Nielsen and Keasling 2011).
This is not an easy task, as inserting a new synthetic path may
lead to a sudden drain of a precursor metabolite, from which a number of metabolites is produced. Thus, it
may be expected that the initial yield and productivity after reconstruction is low, and the flux has to be
redirected toward the desired product.
The production of plant-derived natural products is challenging due to the complexity of the compounds but
also to the complexity of their native production hosts (Li and Pfeifer 2014). Synthetic biology offers the
possibility to overcome these hurdles by designing biosynthesis pathways in heterologous host. The main
challenges if a pathway is adapted to be expressed in a heterologous host (e.g. a plant biosynthetic pathway in
microbes) are the necessity to have genetic sequence information, proper design of sequence information for
active gene expression, biosynthesis and improved production metrics (Li and Pfeifer 2014). These limitations
are due to the fact that the majority of tools and techniques cannot be transferred
between hosts and that the
functioning of parts and modules depends on the cellular context. For example the abundance of RNA