# Nature-Inspired Enzymatic Cascades: Emerging Strategies for Sustainable Chemistry

**Authors:** Eliana Capecchi, Elisabetta Tomaino, Giulia Onnelli, Valentina Ubertini, Raffaele Saladino

PMC · DOI: 10.3390/molecules31040603 · 2026-02-09

## TL;DR

This paper explores how enzyme-based chemical reactions inspired by natural processes can create sustainable and efficient methods for making chemicals.

## Contribution

The paper introduces new strategies combining enzymatic cascades with advanced immobilization and hybrid catalytic systems for sustainable chemistry.

## Key findings

- Enzymatic cascades reduce the need for intermediate isolation and improve reaction selectivity.
- Immobilization on renewable supports enhances enzyme stability and recyclability.
- Hybrid systems with enzymes and non-biological catalysts expand chemical synthesis possibilities.

## Abstract

Enzymatic cascades, defined here as multi-enzymatic sequences operating on a shared reaction pathway and inspired by the spatial and temporal organization of metabolism, have emerged as powerful and versatile tools for sustainable organic synthesis. They minimize intermediate isolation, enhance atom economy and ensure outstanding chemo-, regio- and stereoselectivity, providing efficient alternatives to conventional multistep routes. Here, we highlight the conceptual role of substrate channeling, minimal cells, artificial metabolism and enzyme promiscuity in the translation of enzymatic cascades into synthetic strategies. Special attention is focused on advanced immobilization on functional and renewable supports, which enhance stability and recyclability and introduce new ways for thermodynamic and kinetic control. Hybrid systems integrating enzymes with photocatalysis, electrochemistry and chemical modules expand the catalytic repertoire far beyond biology. Complementary tools in bioinformatics, structural modeling and artificial intelligence may also enable pathway balancing, predictive design and dynamic optimization. Applications span from the valorization of renewable feedstocks to the synthesis of privileged scaffolds and fine chemicals.

## Full-text entities

- **Genes:** Alcohol dehydrogenase [NCBI Gene 13909458]
- **Diseases:** Neisseria meningitidis (MESH:D006069), ET (MESH:D016751), injury to (MESH:D014947)
- **Chemicals:** nucleoside (MESH:D009705), diols (MESH:D011276), agarose (MESH:D012685), melanin (MESH:D008543), sesquiterpene (MESH:D012717), biochar (MESH:C540010), ABTS (MESH:C002502), lactone (MESH:D007783), TiO2 (MESH:C009495), CO2 (MESH:D002245), AlCl3 (MESH:D000077410), farnesyl pyrophosphate (MESH:C004808), FMN (MESH:D005486), vidarabine (MESH:D014740), viologen (MESH:D014755), lignin (MESH:D008031), quinoline (MESH:C037219), ATP (MESH:D000255), reactive oxygen species (MESH:D017382), methyl viologen (MESH:D010269), molnupiravir (MESH:C000656703), formaldehyde (MESH:D005557), ethyl 4-chloroacetoacetate (MESH:C111982), glucose (MESH:D005947), flavonoid (MESH:D005419), amorpha-4,11-diene (MESH:C515348), alcohol (MESH:D000438), epoxides (MESH:D004852), hydrogen (MESH:D006859), quinone (MESH:C004532), flavin (MESH:C024132), oleic acid (MESH:D019301), gallium (MESH:D005708), NAD+ (MESH:D009243), PBS (MESH:D007854), glycerol (MESH:D005990), imine (MESH:D007097), betaine (MESH:D001622), atorvastatin (MESH:D000069059), Pluronic F-127 (MESH:D020442), norcoclaurine (MESH:C012348), amino alcohols (MESH:D000605), pyrrolidine (MESH:C032519), ITO (MESH:C109984), pregabalin (MESH:D000069583), H2O2 (MESH:D006861), (R)-arylpropanols acids (-), tyrosol (MESH:C011867), (S)-CHBE (MESH:C121244), 2-MeTHF (MESH:C587233), fatty acid (MESH:D005227), 1,2-phenylenediamines (MESH:C034193), D-glucono-1,5-lactone (MESH:C010730), lipoamide (MESH:C013091), amine (MESH:D000588), phenols (MESH:D010636), quinolones (MESH:D015363), flavanones (MESH:D044950), NADP+ (MESH:D009249), heme (MESH:D006418)
- **Species:** Lentilactobacillus kefiri (species) [taxon 33962], Agrobacterium tumefaciens (species) [taxon 358], Pseudomonas putida (species) [taxon 303], Mucor javanicus (species) [taxon 51122], Neisseria meningitidis (species) [taxon 487], Colletotrichum graminicola (species) [taxon 31870], Acinetobacter calcoaceticus (species) [taxon 471], Homo sapiens (human, species) [taxon 9606], Moesziomyces antarcticus (species) [taxon 84753], Komagataella pastoris (species) [taxon 4922], Chlorella variabilis (species) [taxon 554065], Aspergillus nidulans (species) [taxon 162425], Geobacillus stearothermophilus (species) [taxon 1422], Escherichia coli (E. coli, species) [taxon 562], Agaricus bisporus (common mushroom, species) [taxon 5341], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Aspergillus oryzae (species) [taxon 5062], Agrocybe aegerita [taxon 5400]

## Figures

14 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943553/full.md

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Source: https://tomesphere.com/paper/PMC12943553