New Emerging Bio-Catalysts Design in BiotransformationsReview
Biotechnol. Adv. 2015, 33, 605-613, 10.1016/j.biotechadv.2014.12.010
The development of new and successful biotransformation processes of key interest in medicinal and pharmaceutical chemistry involves creating new biocatalysts with improved or even new activities and selectivities. This review emphasizes the new emerging developed strategies to achieve this goal, site-selective chemical modification of enzymes using tailor-made peptides, specific insertion of metals or organometallic complexes into proteins producing bio-catalysts with multiple activities and computational design for creating evolved artificial enzymes with non-natural synthetic catalytic activities.
Preparation of an Immobilized Lipase-Palladium Artificial Metalloenzyme as Catalyst in the Heck Reaction: Role of the Solid Phase
Adv. Synth. Catal. 2015, 357, 2687-2696, 10.1002/adsc.201500014
A p‐nitrophenylphosphonate palladium pincer was synthesized and selectively inserted by irreversible attachment on the catalytic serine of different commercial lipases with good to excellent yields in most cases. Among all, lipase from Candida antarctica B (CAL‐B) was the best modified enzyme. The artificial metalloenzyme CAL‐B‐palladium (Pd) catalyst was subsequently immobilized on different supports and by different orienting strategies. The catalytic properties of the immobilized hybrid catalysts were then evaluated in two sets of Heck cross‐coupling reactions under different conditions. In the first reaction between iodobenzene and ethyl acrylate, the covalent immobilized CAL‐B‐Pd catalyst resulted to be the best one exhibiting quantitative production of the Heck product at 70 °C in dimethylformamide (DMF) with 25% water and particularly in pure DMF, where the soluble Pd pincer was completely inactive. A post‐immobilization engineering of catalyst surface by its hydrophobization enhanced the activity. The selectivity properties of the best hybrid catalyst were then assessed in the asymmetric Heck cross‐coupling reaction between iodobenzene and 2,3‐dihydrofuran retrieving excellent results in terms of stereo‐ and enantioselectivity.
Metal: PdLigand type: Thioether (Pincer complex)Host protein: Lipase B from C. antarctica (CALB)Anchoring strategy: CovalentOptimization: Chemical & geneticReaction: Heck cross-couplingMax TON: ~4160ee: 96PDB: ---Notes: ArM is immobilized on Sepabeads.