5.4 Helper Functions 89metabolism, replication, and transcription is likely to have considerable bearing
on the genome organization within the cell (it is at the root of the preservation
of a nucleus in eukaryotes).
The genome backbone phosphate is not strictly universal. Some organisms
use a variant where the usual phosphate group is phosphorothiolated [42]. This
modification, which can be used for specific recognition/folding processes and
provides the cells with a protection against oxidative stress [43], is a first hint that
SynBio could evolve toward xenobiology (i.e., the use of nonstandard building
blocks for the construction of synthetic cells [44]). A further indication of this
possibility is the presence of diaminopurine instead of adenine is some cyano
phages [45]. Finally, de Crécy‐Lagard and coworkers showed that a 7‐deazapu
rine derivative can replace guanine in functional DNA [46]. Knowing that DNA
methylation can be used to control gene expression [47], the idea that other
modifications may have a similar role is straightforward. A track for the future
analysis of the distribution of phosphorothiolated sites or input of 7‐deazagua
nines has not yet been undertaken, and their role in gene expression is not
known. In general, there is still considerable room for exploring the presence and
role of nucleic acid modifications [48].
Amino acids make the primary sequence of proteins, while many more exist in
metabolic pathways (be it only as the result of catabolism of posttranslationally
modified proteins). Proteinogenic amino acids are far from random, however, as
several are fairly easy to synthesize (the smallest ones) and can be converted into
one another at low energy cost [49], while they are split into three major physico
chemical properties highly relevant to water as a universal albeit physically unusual
OMP UMP UDPUTP CTPdCDP dCTPmRNA
PNPase
CDP
CMPATPADP
RNasesdUDP dUTP dUMP dTMPPPi
dTDPdTTP2 PiDNA
Figure 5.3 Excerpt of the metabolism of pyrimidines and DNA synthesis. The building blocks
for DNA stem from NDPs, not nucleoside triphosphates (NTPs). This creates an imbalance in
the case of cytosine, because CDP is not produced during the de novo synthesis. This explains
why, in general, C is the limiting nucleotide, driving A+T enrichment of the genome in most
situations. Nucleoside diphosphokinase is reversible; however ATP is in excess over adenosine
diphosphate (ADP), so that production of CDP is limiting via this route. CDP comes mainly
from mRNA turnover via phosphorolysis (polynucleotide phosphorylase) or RNase activity,
with further phosphorylation using cytidylate kinase.