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Updated: Jun 16, 2026
09:14
Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Mechanistic Insights into Lysine Cyclodeaminase Catalysis
Yao Wei1, Beatrice Rassati2, Uliano Guerrini1
1Dipartimento di Scienze Farmacologiche e Biomolecolari "Rodolfo Paoletti", Università degli Studi di Milano, Via Giuseppe Balzaretti 9, 20133 Milano, Italy.
ACS Omega
|June 15, 2026
Summary
Lysine cyclodeaminase (LCD) efficiently converts l-lysine but struggles with bulkier derivatives. Steric and dynamic constraints, not substrate access, limit catalysis of esterified substrates, guiding future enzyme engineering.
Area of Science:
- Biocatalysis
- Enzyme engineering
- Computational chemistry
Background:
- Lysine cyclodeaminase (LCD) is industrially important for producing l-pipecolic acid from l-lysine.
- LCD exhibits a narrow substrate scope, limiting its application with modified substrates like l-lysine ethyl ester.
Purpose of the Study:
- To elucidate the molecular basis of LCD's substrate selectivity.
- To define the catalytic mechanism and identify constraints limiting activity on bulkier substrates.
Main Methods:
- Molecular docking and classical molecular dynamics simulations.
- Well-tempered metadynamics simulations and experimental validation.
- Substrate tunnel engineering of LCD variants.
Main Results:
- Both l-lysine and l-lysine ethyl ester bind to the LCD active site.
- Engineered LCD variants showed improved tunnel properties but no enhanced activity on esterified substrates.
- Mechanistic simulations revealed steric and dynamic constraints hinder cyclization of the l-lysine ethyl ester iminium intermediate.
Conclusions:
- Enzyme dynamics and steric/dynamic constraints, not substrate access, dictate LCD's selectivity for esterified substrates.
- A mechanistic framework linking enzyme dynamics, substrate recognition, and efficiency was established.
- Findings provide a basis for rational engineering of LCD to broaden substrate scope for industrial applications.
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