Exploiting Biocatalysis in the Synthesis of Supramolecular Polymers - Enzymatic Polymerisation - page 128

[ 17 ] as well as muscle contraction in higher organisms. Actin filaments are linear
polymers of the monomeric subunit globular actin (G-actin), which undergo contin-
uous polymerisation and depolymerisation. This process is initiated and controlled
by the enzymatic hydrolysis of the biomolecular fuel molecule adenosine triphos-
phate (ATP) to the diphosphate analogue (ADP) by ATPase (Fig. 1 b ). Likewise, the
on-demand formation of microtubules, which are responsible for intracellular trans-
port and cell division during mitosis, is regulated by enzymatic reactions. Here,
the enzymatic hydrolysis of guanosine triphosphate (GTP) to GDP by GTPase con-
trols the corresponding assembly and dis-assembly of the monomeric proteins in
microtubules (Fig. 1 c ) [ 17 ] . In summary, Nature has evolved a number of dynamic
polymeric structures that can form and dissociate under enzymatic control. These
play key roles as dynamic intra- and extracellular structures that underlie dynamic
cell function. Scientists are interested in copying these highly dynamic processes in
man-made systems, as detailed in the following sections.

3 Enzymatic Supramolecular Polymerisation

Building blocks (monomers) for enzyme-controlled supramolecular polymeri-
sations are comprised of three components: (1) an enzyme-specific target (bio-
molecule based on the enzyme's substrate specificity), (2) a self-assembly
component that directs the non-covalent interaction responsible for supramolec-
ular polymerisation, and (3) a molecular switch component that prevents precursor
self-assembly and activates self-assembly upon enzyme action.

3.1 Enzyme-Specific Target

A range of enzyme-catalysed reactions have been exploited to control forma-
tion of supramolecular polymeric structures [ 11 , 18 ] . These include enzymatic
crosslinking strategies using protein crosslinking enzymes such as transglutami-
nase [ 19 , 20 ], enzymatic production of gelators from non-gelling precursors using
protease [ 21 - 24 ] , esterase [ 22 ], penicillin G amidase [ 25 ] , trans-acylase [ 26 ]and
phosphatase [ 27 - 30 ] activities. The opposite process, i.e. enzymatic degradation
or disassembly of supramolecular structures, has been described in the context of
degradable peptide nanotubes [ 31 - 33 ] , combined with enzymatically or thermally
controlled release [ 34 ], and cell culture matrices [ 35 , 36 ] .
Dynamic systems that exploit both assembly and dis-assembly have been ex-
plored using reversible (de)phosphorylation in response to kinases (phosphorylation
enzymes) and phosphatases [ 28 , 37 ] . In these systems, the phosphorylation reac-
tion is facilitated by simultaneous hydrolysis of ATP, akin to biological systems
discussed in the previous section. The concentration of ATP can dictate the pre-
ferred direction of these reactions, with phosphorylation levels (and therefore