The halo-substituent effect on Pseudomonas cepacia lipase-mediated regioselective acylation of nucleosides: A comparative investigation

• Published in: Journal of biotechnology 2015-10, Vol.212, p.153-158
• Main Authors: Wang, Zhao-Yu, Bi, Yan-Hong, Yang, Rong-Ling, Duan, Zhang-Qun, Nie, Ling-Hong, Li, Xiang-Qian, Zong, Min-Hua, Wu, Jie
• Format: Article
• Language: English
• Subjects: Acylation; Biotechnology; Burkholderia cepacia - enzymology; Catalysis; Chains; Enzymatic acylation; Enzymes, Immobilized - chemistry; Enzymes, Immobilized - metabolism; Halo-substituent recognition; Halogens; Hydrophobicity; Lipase; Lipase - chemistry; Lipase - metabolism; Nucleoside modification; Nucleosides; Nucleosides - metabolism; Pseudomonas; Pseudomonas cepacia; Pseudomonas cepacia lipase; Stereoisomerism; Substrate Specificity
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/j.jbiotec.2015.08.027

•Nucleosides possessing different halogen atoms could be successfully converted into their corresponding esters derivatives catalyzed by PCL lipase.•The physicochemical properties of the halo-substituents in nucleosides profoundly influenced the enzyme’s behavior.•The position (2′- vs. 5-position) of the substituents was also found to be another vital factor for all acylations.•PCL exhibited the highest 3′-regioselectivity toward the long-chain vinyl donor (C14) as compared to shorter (C10 and C6) ones. In this work, comparative experiments were explored to investigate the substrate specificity of Pseudomonas cepacia lipase in regioselective acylation of nucleosides carrying various substituents (such as the H, F, Cl, Br, I) at 2′- and 5-positions. Experimental data indicated that the catalytic performance of the enzyme depended very much on the halo-substituents in nucleosides. The increased bulk of 2′-substituents in ribose moiety of the nucleoside might contribute to the improved 3′-regioselectivity (90–98%, nucleosides a–d) in enzymatic decanoylation, while the enhancement of regioselectivity (93–99%) in 3′-O-acylated nucleosides e–h could be attributable to the increasing hydrophobicity of the halogen atoms at 5-positions. With regard to the chain-length selectivity, P. cepacia lipase displayed the highest 3′-regioselectivity toward the longer chain (C14) as compared to shorter (C6 and C10) ones. The position, orientation and property of the substituent, specific structure of the lipase’s active site, and acyl structure could account for the diverse results.