5.4 Helper Functions 91This metabolic constraint must be taken into account when planning to derive
novel nucleic acid analogs for next‐generation SynBio.
At a more integrated level of the hierarchical organization of life, multicellular
organisms have developed an extraordinary diversity of macromolecular materi
als that work as frames, protectants, buffers, motors, signals, traps, and so on.
DNA itself is known to belong to the structural polyanionic polymers, as it is, for
example, a component of biofilms [61], which introduces a fitness property that
has nothing to do with its coding capacity. We have seen that there is anyway a
significant selection pressure to increase its length in order to match its synthesis
with that of the bulk of the cell (see Section 5.4.3). Exploration of chemical diver
sity both in terms of small metabolites (see, e.g., [62–64]) and in terms of macro
molecules is expected to develop considerably (see, e.g., [65–67]) in the next
decade. The corresponding genetic program implementation within the cell will
need to be explored in depth. Here again thinking as an engineer will come as an
asset for innovation.
The list of engineering constraints on the matter used in living organisms is
unlimited. The examples presented earlier are just meant to illustrate the way we
should presently consider metabolism. In another dimension, metabolites of
industrial interest, such as isobutene, are and will be produced by reprogram
ming and setting up synthetic pathways [68]. This will entail production of mol
ecules that may react with components of existing cell components, including
DNA. To end up with high yields, metabolic engineering will need a deep reflec
tion on metabolite reactivity within the confined medium of the cell, a topic that
has mostly been restricted to the study of reactive oxygen species [69]. In par
ticular it seems obvious that the chromosome must be protected, as much as
possible, against reactive metabolic intermediates (we saw previously that phos
phorothioation is a solution uncovered during evolution). Management of waste
will also be a major topic to be developed (be it only to limit carbon dioxide
production).
5.4.2 Energy
Management of energy is central to life. It has long been established to be associ
ated with electron and proton transfers and with storage as energy‐rich phosphate
bonds. The motto “better lose energy than control” seems to dominate life. Much
is known about the energy‐related processes, but much also remains to be under
stood in terms of optimization. For example, despite their ubiquity (all cells con
tain these compounds), the role of polyphosphates has seldom been considered,
despite their importance for energy management, regulation, and storage [70–72].
It seems likely that their contribution as the ultimate energy source (polyphos
phates are minerals, hence particularly resistant to desiccation, radiations, and
harsh environments) needs to be reconsidered, especially in terms of synthesis
and usage during transition states, aging, and stresses [28]. Nucleic acids are also
energy‐rich molecules. This implies that some regions of DNA might in fact
have a role as energy stores, besides their expected role in space management,
gene coding, and regulation. In this respect, some organisms have a genome of
huge size [73], without any apparent direct link with its coding capacity.