# Enzymatic Synthesis of Biobased Polyesters and Polyamides
## 7 Enzyme-Catalyzed Synthesis of Polyamides  
Lipases, proteases and other enzymes are capable of catalyzing the formation of amide bonds and therefore, they are suitable enzymes for the in vitro polyamide synthesis [206]. In the following discussion of this section, we focus on the lipase-catalyzed polymerization of synthetic polyamides.  
Similar to the biocatalytic polyester synthesis, the lipase-catalyzed polyamide synthesis can proceed via three basic modes: (1) step-growth polycondensation of diacid/diesters and diaminesor \(\omega\)-amino carboxylic acids/esters; (2) ring-opening polymerization of lactams; and (3) a hybrid of step-growth polycondensation and ring-opening polymerization.  
Two basic modes of elemental reactions are commonly used in the biocatalytic polyamide synthesis: directly amidation and transamidation (aminolysis) (Scheme 17).  
The lipase-catalyzed polymerization of polyamides has not been well studied [208]. This could be attributed mainly to two reasons: (1) the high \(T_{\rm m}\) of polyamides, and (2) the poor solubility of polyamides in common organic solvents. On the one hand, polyamides like nylons and TPA-based polyamides are semi-crystalline polymers which normally possess a high \(T_{\rm m}\) above 100 \({}^{\circ}\)C. At such elevated temperatures, the catalytic reactivity of lipases is significantly decreased due to the occurrence of protein denaturation and deactivation. On the other hand, many polyamides can be only dissolved in some aggressive solvents such as formic acid, concentrated H\({}_{2}\)SO\({}_{4}\), and trifluoroacetic acid, in which lipases cannot act.  
Nevertheless, some oligoamides and polyamides are successfully produced via the lipase-catalyzed polymerization [206; 207; 208]. Some typical examples are given below.  
[PERSON] et al. [230; 231] investigated the lipase-catalyzed polymerization of diamines and diesters in bulk (Scheme 18), which resulted in aliphatic polyamides with \(\overline{M_{\rm w}}\)'s of around 3000-15,000 g/mol. This is the first report showing that high molecular weight polyamides can be produced from lipase-catalyzed polymerization.  
The CALB-catalyzed ring-opening polymerization of \(\varepsilon\)-caprolactone was reported by [PERSON] et al. [232]. They claimed that the enzymatic ring-opening polymerization gave nylon 6 with a high \(\overline{M_{\rm w}}\) of 212,000 g/mol.  
Aliphatic polyamides such as nylon 6,13, nylon 8,13 and nylon 12,13 were synthesized via the N435-catalyzed ring-opening addition-condensation (Scheme 19) [197]. The \(\overline{M_{\rm n}}\)'s of the resulting nylons were around 5600-8300 g/mol.  
Figure 17: Basic modes of elemental lipase-catalyzed reactions in biocatalytic polyamide synthesis.  
In our group, enzymatic polymerization of polyamides is one of the focused research area. For example, the enzymatic polymerization of 2-azetidinone was first studied in our laboratory (Scheme 20) [233]. A different mechanism for the enzymatic ring-opening polymerization of \(\beta\)-propiolactam was revealed and a catalytic cycle for the oligomerization of \(\beta\)-lactam that rationalizes the activation of the monomers was proposed [234]. Moreover, aliphatic oligoamides [233; 235; 236], semi-aromatic oligoamides [237], and poly(ester amide)s [238] are successfully prepared via lipase-catalyzed polymerization in our laboratory.