Atomistic Model for the Polyamide Formation from beta-Lactam Catalyzed by Candida antarctica Lipase B

Iris Baum, Brigitta Elsaesser, Leendert W. Schwab, Katja Loos, Gregor Fels*, Brigitta Elsässer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)
297 Downloads (Pure)

Abstract

Candida antarctica lipase B (CALB) is an established biocatalyst for a variety of transesterification, amidation, and polymerization. reactions. In contrast to polyesters, poly amides are not yet generally accessible via enzymatic polymerization. In this regard, an enzyme-catalyzed ring-opening polymerization of beta-lactam (2-azetidinone) using CALB is the first example of an enzymatic polyamide formation yielding unbranched poly(beta-alanine), nylon 3. The performance of this polymerization, however, is poor, considering the maximum chain length of 18 monomer units with an average length of 8, and the molecular basis of the reaction so far is not understood. We have employed molecular modeling techniques using docking tools, molecular dynamics, and QM/MM procedures to gain insight into the mechanistic details of the various reaction steps involved. As a result, we propose a catalytic cycle for the oligomerization of beta-lactam that rationalizes the activation of the monomer, the chain elongation by additional beta-lactam molecules, and the termination of the polymer chain. In addition, the processes, leading to a premature chain termination are studied. Particularly, the QM/MM calculation enables an atomistic description of all eight steps involved in the catalytic cycle, which features an in situ-generated beta-alanine as the elongating monomer and which is compatible with the experimental findings.

Original languageEnglish
Pages (from-to)323-336
Number of pages14
JournalACS Catalysis
Volume1
Issue number4
DOIs
Publication statusPublished - Apr-2011

Keywords

  • Candida antarctica lipase B
  • enzyme catalysis
  • beta-lactam ring-opening
  • molecular modeling
  • enzymatic polymerization
  • enzyme acylation
  • RING-OPENING POLYMERIZATION
  • PROTEIN-LIGAND COMPLEXES
  • EPSILON-CAPROLACTONE
  • POLYESTERS
  • LACTONES
  • PREDICTION
  • RESOLUTION
  • MECHANISM
  • KINETICS
  • SOLVENT

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