Enzyme catalysis lactones

The copolymerization of lactones took place through enzyme catalysis [92]. The copolymerization of e-CL with d-VL catalyzed by lipase PF affords the corresponding copolymer having a molecular weight of several thousand. From 13C NMR analysis, the copolymer was found to be of random structure having both units, suggesting the frequent occurrence of transesterifications between the polyesters. In the copolymerization of 8-OL with e-CL or DDL, random copolyesters were also formed [84], whereas the copolymer from e-CL and PDL was not statistically random [88]. 

Ester copolymers were synthesized by lipase-catalyzed copol5mierization of lactones, divinyl esters, and glycols (177). The nmr analysis showed that the resulting product was not a mixture of homopolymers, but a copolymer derived from the monomers, indicating that two different modes of pol5mierization, ringopening polymerization and polycondensation, simultaneously take place through enzyme catalysis in one pot to produce ester copolymers. 

AT,r,=41 0.7 IIM. These rates were also pH dependent, with Ka = 6.58, in reasonable agreement with the catalytic Ka value for a serine protease. The actual inactivation rate was determined from rescue experiments. At various times t following addition of suicide substrate inhibitor to enzyme, 10 vaM of the nucleophile )6-mercaptoethanol was added. This nucleophile reacted rapidly with excess ynenol lactone, allowing any enzyme not inactivated to deacylate to regenerate active enzyme, as shown in Fig. 13.2. The inactivation rates were also saturable, giving 4 or /Tinact = 0.0037 0.0001 s and inact = 0.63 0.08 (xM. Gel filtration of the enzyme-inhibitor mixture before full inactivation could occur, followed by dilution into assay conditions, allowed determination of the deacylation rate, 3 = 0.0056 s The pH dependence of this rate was also determined and found to have a Ka value of 7.36. This value was in excellent agreement with the catalytic p a value, providing further evidence for the role of enzyme catalysis in the mechanism of inactivation. 

Water was used as solvent for the first time in the lipase-catalyzed ROP of five lactone monomers, e-CL, OL, UDL, DDL, and PDL (Scheme 5) [69, 70]. Macrolides of UDL, DDL, and PDL are less reactive than lactones of smaller ring size due to lower ring strain when using a usual chemical catalyst [71]. However, they showed higher reactivity in enzyme catalysis and were polymerized by lipase in water to produce the corresponding polyesters typically, UDL gave polyUDL with 1,300 (Mw/M = 2.1) in 79% yields at 60°C for 72 h. DDL is... 

Warner, M. C., Nagendiran, A., Bogar, K., and Backvall, J.-E. (2012). Enantioselective route to ketones and lactones from exocyclic allylic alcohols via metal and enzyme catalysis. Org. Lett, 14,5094-5097. 

In Sect. 7.6, we examined the hydrolysis of lactones. Emphasis was placed on the reversibility of the reaction and the possibility of both chemical and enzymatic catalysis. Some enzymes active in lactone hydrolysis and the hydrolytic inactivation of a number of pharmacologically active lactones were discussed. 

Increasing the substrate range of an enzyme could be thought of as improving a promiscuous activity. However, here we will use a more strict definition in which a promiscuous activity involves catalysis of a reaction with a different class of substrate. Many enzymes are promiscuous in the sense that they can catalyze other reactions. This is not surprising considering that the enormous variety of enzymes that exist utilize only a small number of active site chemistries and structural scaffolds. Thus, an almost identical enzyme could catalyze lactone hydrolysis or phosphotriester hydrolysis. Because these activities are often very weak to begin with, directed molecular evolution experiments to improve these activities often result in remarkable improvements. 

Paraoxonase enzymes clearly belong to a distinct enzyme family.11,19 They are not serine or cysteine proteases but instead use divalent metal ion for catalysis. The enzymes have limited substrate specificity but do hydrolyze a variety of aromatic and aliphatic lactones, including several statin lactones.20... 

A pantothenic acid hydrolase (pantothenase) activity has been isolated from Pseudomonas fluorescens and other Pseudomonas strains. This enzyme hydrolyzes the amide bond of pantothenic acid 2 to form pantoic acid 5 (or pantoyl lactone) and /i-alanine 7 (EC 3.5.1.22) (Equation (10)). A detailed kinetic study of the reaction mechanism has shown that the reaction is partially reversible because of the formation of an acyl—enzyme (pantoyl-enzyme) intermediate during the course of catalysis, which may react with either water or / -alanine to form pantoic acid (the product hydrolysis) or pantothenic acid (the original substrate) Such a mechanism suggests that this enzyme could act as a pantothenate synthase, as reaction of the active site serine with pantoyl lactone would result in the formation of the pantoyl—enzyme intermediate. However, no biochemical or genetic evidence is currently available to support such a hypothesis. 

---