Lipases Serratia marcescens

S,3 R)-3-(4-Melhoxyphenylglycidic add) methyl ester Lipase Serratia marcescens... 

An example of an industrial membrane bioreactor is the hollow-fiber membrane system for the production of (-)-MPGM (3-(4-methoxyphenyl)glycidic acid methyl ester), which is an important intermediate for the production of diltiazem hydrochloride [81, 82]. For the enantiospecific hydrolysis of MPGM a hollow-fiber ultrafiltration membrane with immobilized lipase from Serratia marcescens is used. (-f)-MPGM is selectively converted into (2S,3J )-(-F)-3-(4-methoxyphenyl)glyci-dic acid and methanol. The reactant is dissolved in toluene, whereas the hydrophilic product is removed via the aqueous phase at the permeate side of the membrane, see Fig. 13.9. EnantiomericaUy pure (-)-MPGM is obtained from the to-... 

Matsumae, H., Fumi, M., Shibatani, T. and Tosa. T. (1994) Prodnction of optically-active 3-phenylglycidyl acid ester by the lipase from Serratia marcescens on a hollow-fiber membrane reactor. Journal ofEermentation and Bioengineering, 78(1), 59-64. 

An alternative approach is to perform a resolution of the epoxy ester (10), which can be accomplished with a lipase from Serratia marcescens (Scheme 2) [30,31]. This approach allows for resolution of an early intermediate that can then be used to prepare just the desired diastereoisomer. Alternatives are to resolve precursors to the epoxy functionality [32]. 

Kinetic Resolution of Clycidic Acid Methyl Ester by Lipase from Serratia marcescens (E.C. 3.1.1.3) 50-531... 

The lipase from Serratia marcescens has a high enantioselectivity (E = 135) for the (2R,3S)-(4-methoxyphenyl) glycidic acid methyl ester, which acts as a competitive inhibitor. The formed acid (hydrolyzed (+)-methoxyphenylglycidate) is unstable and decarboxylates to give 4-methoxyphenylacetaldehyde this aldehyde strongly inhibits and deactivates the enzyme. It is removed by transfer to the aqueous phase by formation of a water-soluble adduct with sodium hydrogen sulfite added to the aqueous phase. The bisulfite acts also as a buffer to maintain constant pH during synthesis. 

H. Matsumae, T. Shibatani, Purification and characterization of the lipase from Serratia marcescens Sr41 8000 responsible for asymmetric hydrolysis of 3-phenylglycidic acid esters, J. Ferment. Bioeng. 1994, 77, 152-158. 

T. Shibatani, K. Omori, H. Akatsuka, E. Kawai, H. Matsumae, Enzymatic resolution of diltiazem intermediate by Serratia marcescens lipase molecular mechanism of lipase secretion and its industrial application J. Mol. Cat. B. Enz. 2000, 10,141-149. 

Production of an optically active diltiazem intermediate (2R, 3S)-methoxyophenylglyci-date methyl ester ((-)-MPGM) from racemic MPGM by the action of lipase from Serratia marcescens in a toluene aqueous biphasic system (Tanabe Seiyaku Co., Ltd.). For the continuous production of (-)-MPGM, a hollow fiber bioreactor was set up in collaboration with Sepracor Inc. The introduction of this enzymatic step allowed the shortening of the diltiazem synthesis from nine down to five steps. 

Lipases used in laundry detergents and in other bulk applications do not require enzyme immobilization however, an increasing number of applications in synthesis and biotransformation demand an immobilized biocatalyst for efficient use. It has been claimed that the success of a lipase catalyzed biotransformation for the production of certain pharmaceuticals depends on immobilization. For example, in the industrial preparation of the chiral intermediate used in the synthesis of Diltiazem, the lipase from Serratia marcescens was supported in a spongy matrix, which was used in a two-phase membrane bioreactor (Cowan 1996). 

---