Recent advances in harnessing PLP-dependent enzymes for biocatalytic C-C bond formation
Related Experiment Video
Updated: Oct 30, 2026

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
Weiwei Chai1, Anirudh Lahiri2, Yang Hai1
1Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA, 93106, United States.
Abstract:
Pyridoxal 5'-phosphate (PLP)-dependent enzymes are among the most versatile biocatalysts in nature and have long been recognized for their central roles in amino acid metabolism. Recent advances in enzyme discovery, mechanistic enzymology, and protein engineering have substantially expanded the synthetic repertoire of PLP-dependent enzymes beyond their native functions. In this review, we highlight recent advances (2024-2026) in PLP-dependent C-C bond-forming biocatalysis, including aldol-type additions, Mannich-type additions, nucleophilic substitution (SN2) reactions, β- and γ-substitution reactions, [3+2] annulations, and radical alkylations. Together, these studies illustrate how enzyme discovery and engineering have transformed PLP-dependent enzymes into versatile platforms for reaction discovery and asymmetric synthesis, while revealing new opportunities for expanding the reactivity landscape of PLP catalysis.
Related Concept Videos
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
Olefin Metathesis Polymerization: Overview
Ruthenium-based Grubbs catalyst is the most commonly used catalyst for olefin metathesis polymerization. Grubbs catalyst consists of a...
Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
Cycloaddition Reactions: Overview
Aldehydes and Ketones to Alkenes: Wittig Reaction Mechanism
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
