# Roles of D-Amino Acids on the Bioactivity of Host Defense Peptides
## 8 Synthesis of d-AA-Containing HDPs  
d-AA-containing HDPs could be produced by chemical synthesis or enzymatic synthesis [12]. In the former approach, d-AA can be produced via chiral resolution of l-amino acids or by asymmetric synthesis from chiral or prochiral starting materials. The inherent racemization of d-AA leads to low yields and high cost thereby making chemical synthesis unfavorable. Enzymatic synthesis have thus been proposed to be a promising approach for producing d-AA with high optical purity as well as being cost-efficient and environmental friendly. Briefly, enzymatic synthesis of d-AA can be carried out using three major classes of enzymes namely hydrolases, oxidoreductases and d-amino acid aminotransferases [12]. Several enzymes are involved in the synthesis of d-AA via the hydrolase enzymes consisting of d-hydantoinase coupled with \(N\)-carbamoyl-d-amino acid amidohydrolase, \(N\)-acyl-d-amino acid amidohydrolase, d-amino acid amidase and d-amino peptidase. Firstly, a two-step catalysis of the starting material dl-5-substituted hydantoinas via d-hydantoinase coupled with \(N\)-carbamoyl-d-amino acid amidohydrolase have been successfully applied for d-AA production at the industrial scale [125]. This methods have been used to produce a wide range of d-AA including D-phenylglycine, d-\(p\)-hydroxyphenylglycine, d-Trp, d-Phe, d-Val, d-Ala and d-Met [126]. Secondly, hydrolysis of \(N\)-acyl-d-amino acid via \(N\)-acyl-d-amino acid amidohydrolase is the most useful and convenient reaction for producing d-AA. Products obtained from this method includes fatty acid and corresponding d-AAs comprising of d-Ala, d-Arg, d-Asp, d-Glu and d-Leu [17]. Thirdly, d-amino acid amidase can catalyze the stereospecific hydrolysis of d-AA amide to obtain ammonia and the corresponding d-AAs. This method have been successfully applied in the synthesis of d-phenylalaninamide, d-tyrosinamide, d-leucinamide, d-methionineamide, d-glutaminamide and d-lysinamide [127; 128]. Moreover, other hydrolases targeting peptide substrates were used to produce d-AAs. For example, d-aminopeptidase preferred to catalyze peptide substrates for producing d-Ala with 100% yield and >99% enantiomeric excess [129]. Alkaline d-peptide catalyze peptides that are composed of aromatic d-AAs via hydrolysis reaction of the carboxy-terminal peptide of (d-Phe)\({}_{3}\) and (d-Phe)\({}_{4}\) to produce d-Phe and (d-Phe)\({}_{2}\)[130]. l-amino acid oxidase and d-amino acid dehydrogenase are two important enzymes belonging to the oxidoreductase class. Firstly, l-amino acid oxidase catalyzes the conversion of l-amino acids with strict stereospecificity to produce d-AA via deamination reaction with a maximum of 50% theoretical yield. Comparing with d-hydantoinases and d-aminoacylases, this method gain beneficial of producing d-Glu, d-Arg and d-homoserine. Second, d-amino acid dehydrogenase have been used to produce d-AAs in the presence of NADPH. Synthesis of d-AA against a series of \(\alpha\)-keto acids produces corresponding d-AAs through amination reaction. However, only _meso_-diaminopilemate dehydrogenase from _Symbiobacterium thermophilium_ IAM14863 is able to synthesize d-AA while _meso_-diaminopilemate dehydrogenase from other organisms do not afford the activity to produce d-AA, which limits the potential application of these enzymes for large scale production of d-AAs [12]. d-amino acid aminotransferase is the last class of enzymes involved in d-AA synthesis. The principle of this class relies on the transfer of amino group from d-AA donors to keto-acid acceptors. Many types of keto-acids are used as starting materials and can be utilized to produce d-AAs at different rate of activity by d-amino acid aminotransferase from _Lactobacillus salivarius_[131]. Moreover, the use of a thermostable d-amino acid aminotransferase from _Bacillus_ sp.