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Advances in integrating microbial metabolism with catalytic systems

Nature Chemical Biology (2025)Cite this article

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Abstract

Integrated catalytic systems that combine microbial metabolism with chemocatalysis, electrocatalysis, photocatalysis and biocatalysis are emerging as sustainable solutions for hybrid chemical–biosynthetic production and environmental remediation. By leveraging the strengths of engineered microbial cells and their metabolic pathways, along with synthetic catalysts, these hybrid systems use the unique benefits of each catalytic process to enable complex, efficient transformations, marking a notable advance over conventional methods. This Review highlights the progress in the assembly of hybrid catalytic systems and their application in a range of diverse fields. We examine the advantages of integrating chemocatalysts with whole-cell microorganisms, fabricating bioelectrochemical systems and microbial–photocatalytic integration. We also discuss how metabolic pathways can be harnessed for the sustainable production of higher-value products and pharmaceuticals and discuss how these hybrid systems can reduce costs, eliminate enzyme purification steps and facilitate multistep cascades.

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Fig. 1: Schematic illustration of integrated hybrid catalytic systems that combine chemical, electrochemical, photochemical and enzyme-based processes with microbial components (bacteria, fungi and algae).
Fig. 2: Integrated microbial and chemocatalytic systems for chemical production via waste utilization.
Fig. 3: Bioelectrocatalytic systems for sustainable synthesis integrate microbial and electrochemical processes.
Fig. 4: Photocatalytic–microorganism hybrid systems combine microorganisms with photocatalysts, enhancing pollutant removal and chemical synthesis.
Fig. 5: Integration of microbial systems through heterologous and orthogonal pathways, biocatalytic cascades and hybrid metabolic engineering.
Fig. 6: Valorization of PET degradation products to produce gallic acid, pyrogallol, muconic acid and vanillic acid via the key intermediate protocatechuic acid in metabolically engineered microorganisms.

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References

  1. Ko, Y. S. et al. Tools and strategies of systems metabolic engineering for the development of microbial cell factories for chemical production. Chem. Soc. Rev. 49, 4615–4636 (2020).

    Article  CAS  PubMed  Google Scholar 

  2. Fan, G., Graham, A. J., Kolli, J., Lynd, N. A. & Keitz, B. K. Aerobic radical polymerization mediated by microbial metabolism. Nat. Chem. 12, 638–646 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rubini, R. & Mayer, C. Addicting Escherichia coli to new-to-nature reactions. ACS Chem. Biol. 15, 3093–3098 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nielsen, J., Tillegreen, C. B. & Petranovic, D. Innovation trends in industrial biotechnology. Trends Biotechnol. 40, 1160–1172 (2022).

    Article  CAS  PubMed  Google Scholar 

  5. Sadler, J. C., Dennis, J. A., Johnson, N. W. & Wallace, S. Interfacing non-enzymatic catalysis with living microorganisms. RSC Chem. Biol. 2, 1073–1085 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Luo, Z. W. & Lee, S. Y. Metabolic engineering of Escherichia coli for the production of benzoic acid from glucose. Metab. Eng. 62, 298–311 (2020).

    Article  CAS  PubMed  Google Scholar 

  7. Hua, W. et al. An integrated cofactor and co-substrate recycling pathway for the biosynthesis of 1,5-pentanediol. Microb. Cell Fact. 23, 132 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Werner, A. Z. et al. Lignin conversion to β-ketoadipic acid by Pseudomonas putida via metabolic engineering and bioprocess development. Sci. Adv. 9, eaay1028 (2023).

    Article  Google Scholar 

  9. Zhou, Y., Sekar, B. S., Wu, S. & Li, Z. Benzoic acid production via cascade biotransformation and coupled fermentation biotransformation. Biotechnol. Bioeng. 117, 2340–2350 (2020).

    Article  CAS  PubMed  Google Scholar 

  10. Klumbys, E., Zebec, Z., Weise, N. J., Turner, N. J. & Scrutton, N. S. Bio-derived production of cinnamyl alcohol via a three-step biocatalytic cascade and metabolic engineering. Green Chem. 20, 658–663 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li, H. et al. Integrated electromicrobial conversion of CO2 to higher alcohols. Science 335, 1596 (2012).

    Article  CAS  PubMed  Google Scholar 

  12. Krieg, T., Sydow, A., Faust, S., Huth, I. & Holtmann, D. CO2 to terpenes: autotrophic and electroautotrophic α-humulene production with Cupriavidus necator. Angew. Chem. Int. Ed. Engl. 57, 1879–1882 (2018).

    Article  CAS  PubMed  Google Scholar 

  13. Ganigué, R., Puig, S., Batlle Vilanova, P., Balaguer, M. D. & Colprim, J. Microbial electrosynthesis of butyrate from carbon dioxide. Chem. Commun. 51, 3235–3238 (2015).

    Article  Google Scholar 

  14. Patil, S. A. et al. Selective enrichment establishes a stable performing community for microbial electrosynthesis of acetate from CO2. Environ. Sci. Technol. 49, 8833–8843 (2015).

    Article  CAS  PubMed  Google Scholar 

  15. Xiao, K. et al. Interfacing iodine-doped hydrothermally carbonized carbon with Escherichia coli through an ‘add-on’ mode for enhanced light-driven hydrogen production.Adv. Energy Mater. 11, 2102130 (2021).

    Article  Google Scholar 

  16. Wu, N., Xing, M., Li, Y., Xu, Q. & Li, K. Recent advances in microbe–photocatalyst hybrid systems for production of bulk chemicals: a review. Appl. Biochem. Biotechnol. 195, 1574–1588 (2023).

    Article  CAS  PubMed  Google Scholar 

  17. Luo, B. et al. A periplasmic photosensitized biohybrid system for solar hydrogen production. Adv. Energy Mater. 11, 2003679 (2021).

    Article  Google Scholar 

  18. Wu, C., Tian, K., Guo, X. & Fang, Y. Integrating fermentation engineering and organopalladium chemocatalysis for the production of squalene from biomass-derived carbohydrates. Catalysts 13, 1392 (2023). This approach provides a renewable, high-selectivity platform for squalene production, replacing animal sources and demonstrating smooth microbial-to-chemical process integration.

    Article  CAS  Google Scholar 

  19. Ullmann, L. et al. Improved itaconate production with Ustilago cynodontis via co-metabolism of CO2-derived formate. J. Fungi 8, 1277 (2022). By integrating CO2 hydrogenation with microbial co-metabolism, this study showcases a sustainable routeto high-volume platform chemicals with minimal land-use footprint.

    Article  CAS  Google Scholar 

  20. Wang, J. et al. An efficient chemoenzymatic approach to produce galactose from red macroalgae biomass and its valorization. Biochem. Eng. J. 202, 109179 (2024).

    Article  CAS  Google Scholar 

  21. Liu, Q., Jin, X., Li, H., Ouyang, J. & Zheng, Z. Effective comprehensive utilization strategy for upgrading red seaweed via chemocatalysis and a newly isolated Pseudomonas rhodesiae in tandem. ACS Sustain. Chem. Eng. 11, 3664–3672 (2023).

    Article  CAS  Google Scholar 

  22. Wedde, S. et al. An alternative approach towards poly-ε-caprolactone through a chemoenzymatic synthesis: combined hydrogenation, bio-oxidations and polymerization without isolation of intermediates. Green Chem. 19, 1286–1290 (2017).

    Article  CAS  Google Scholar 

  23. Madhavan, A. et al. Tailoring of microbes for the production of high-value plant-derived compounds: from pathway engineering to fermentative production. Biochim. Biophys. Acta Proteins Proteom. 1867, 140262 (2019).

    Article  CAS  PubMed  Google Scholar 

  24. Liu, X., Ding, W. & Jiang, H. Engineering microbial cell factories for production of plant natural products: from design principles to industrial-scale production. Microb. Cell Fact. 16, 125 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yuan, S. F. & Alper, H. S. Metabolic engineering of microbial cell factories for production of nutraceuticals. Microb. Cell Fact. 18, 46 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Stewart, K. N., Hicks, E. G. & Domaille, D. W. Merger of whole-cell biocatalysis with organocatalysis upgrades alcohol feedstocks in a mild, aqueous, one-pot process. ACS Sustain. Chem. Eng. 8, 4114–4119 (2020).

    Article  CAS  Google Scholar 

  27. Welz, P. J. et al. Integrated biological system for remediation and valorization of tannery wastewater: focus on microbial communities responsible for methanogenesis and sulfidogenesis. Bioresour. Technol. 395, 130411 (2024).

    Article  CAS  PubMed  Google Scholar 

  28. Sadler, J. C. & Wallace, S. Microbial synthesis of vanillin from waste poly(ethylene terephthalate). Green Chem. 23, 4665–4672 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang, H. & Zhou, Q. Bioelectrochemical systems—a potentially effective technology for mitigating microplastic contamination in wastewater. J. Clean. Prod. 450, 141931 (2024).

    Article  CAS  Google Scholar 

  30. Sheldon, R. A. Waste valorization in a sustainable bio-based economy: the road to carbon neutrality. Chemistry 30, e202402207 (2024).

    Article  CAS  PubMed  Google Scholar 

  31. Dong, F. et al. An engineered, non-diazotrophic cyanobacterium and its application in bioelectrochemical nitrogen fixation. Cell Rep. Phys. Sci. 2, 100444 (2021).

    Article  CAS  Google Scholar 

  32. Li, J. et al. A self-assembled MOF–Escherichia coli hybrid system for light-driven fuels and valuable chemicals synthesis. Adv.Sci. 11, e2308597 (2024). This work exemplifies a novel microbial–MOF hybrid system in which light-harvestingmaterials directly boost metabolic flux in engineered microorganisms.

    Article  Google Scholar 

  33. Yu, X. et al. Liquid-liquid phase separation-mediated photocatalytic subcellular hybrid system for highly efficient hydrogen production. Adv. Sci. 11, 2305143 (2024).

    Google Scholar 

  34. Kim, H. T. et al. Biological valorization of poly(ethylene terephthalate) monomers for upcycling waste PET. ACS Sustain. Chem. Eng. 7, 19396–19406 (2019).

    Article  CAS  Google Scholar 

  35. Klos, N. et al. Concatenating microbial, enzymatic, and organometallic catalysis for integrated conversion of renewable carbon sources. JACS Au 4, 4546–4570 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kuang, M. et al. Carbon dioxide upgrading to biodegradable plastics through photo/electrosynthetic biohybrid systems. Angew. Chem. Int. Ed. Engl. 64, e202510123 (2025).

    Article  Google Scholar 

  37. See, W. W. L. & Li, Z. Enantiodivergent functionalization of aryl alkenes into diverse biarylalkanoic acids by integrating biocatalytic cascades with chemocatalysis. ACS Catal. 13, 13215–13224 (2023).

    Article  CAS  Google Scholar 

  38. von Westarp, W. G. et al. Interdisciplinary development of an overall process concept from glucose to 4,5-dimethyl-1,3-dioxolane via 2,3-butanediol. Commun. Chem. 6, 253 (2023). The study offers a blueprint for coupling microbialfermentation with chemical valorization of volatile intermediates in an energy-efficient, modular platform.

    Article  Google Scholar 

  39. Qin, N. et al. Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast. Nat. Commun. 15, 1591 (2024). This work demonstrates how fine-tuning precursor availability and pathway bottlenecks in yeast can create a viable, scalable biochemocatalytic route from CO2 to industrial chemicals.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wallace, S. & Balskus, E. P. Designer micelles accelerate flux through engineered metabolism in E. coli and support biocompatible chemistry. Angew. Chem. Int. Ed. Engl. 55, 6023–6027 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sauer, M. Industrial production of acetone and butanol by fermentation—100 years later. FEMS Microbiol. Lett. 363, fnw134 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kardos, N. & Demain, A. L. Penicillin: the medicine with the greatest impact on therapeutic outcomes. Appl. Microbiol. Biotechnol. 92, 677–687 (2011).

    Article  CAS  PubMed  Google Scholar 

  43. Yoon, Y. J., Kim, E. S., Hwang, Y. S. & Choi, C. Y. Avermectin: biochemical and molecular basis of its biosynthesis and regulation. Appl. Microbiol. Biotechnol. 63, 626–634 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Nielsen, J., Larsson, C., van Maris, A. & Pronk, J. Metabolic engineering of yeast for production of fuels and chemicals. Curr. Opin. Biotechnol. 24, 398–404 (2013).

    Article  CAS  PubMed  Google Scholar 

  45. Li, M. et al. De novo production of resveratrol from glucose or ethanol by engineered Saccharomyces cerevisiae. Metab. Eng. 32, 1–11 (2015).

    Article  PubMed  Google Scholar 

  46. Steen, E. J. et al. Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol. Microb. Cell Fact. 7, 36 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Karaca, H. et al. Metabolic engineering of Saccharomyces cerevisiae for enhanced taxadiene production. Microb. Cell Fact. 23, 241 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhu, Y., Yan, X., Li, W., Qiao, J. & Zhao, G. R. Modular metabolic engineering of Saccharomyces cerevisiae for enhanced production of ursolic acid. J. Agric. Food Chem. 73, 3580–3590 (2025).

    Article  CAS  PubMed  Google Scholar 

  49. Wang, G. et al. Improved biosynthesis of tyrosol by epigenetic modification-based regulation and metabolic engineering in Saccharomyces cerevisiae. J. Biotechnol. 398, 175–182 (2025).

    Article  CAS  PubMed  Google Scholar 

  50. Dong, G. et al. Metabolic engineering of Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids. Metab. Eng. 82, 100–109 (2024). Cyanobacterium S. elongatus PCC 7942 was metabolically engineered with a nitrogenase gene cluster, enabling sunlight-assisted, ambient-condition ammonia synthesis. This work presents a powerful alternative to the Haber–Bosch process, combining photosynthesis and bioelectrosynthesis for sustainable nitrogen fixation.

    Article  CAS  PubMed  Google Scholar 

  51. Yu, W., Cao, X., Gao, J. & Zhou, Y. J. Overproduction of 3-hydroxypropionate in a super-yeast chassis. Bioresour. Technol. 361, 127690 (2022).

    Article  CAS  PubMed  Google Scholar 

  52. Bhagwat, S. S. et al. Sustainable production of acrylic acid via 3-hydroxypropionic acid from lignocellulosic biomass. ACS Sustain. Chem. Eng. 9, 16659–16669 (2021).

    Article  CAS  Google Scholar 

  53. Kim, J. W., Ko, Y., Chae, T. U. & Lee, S. Y. High-level production of 3-hydroxypropionic acid from glycerol as a sole carbon source using metabolically engineered Escherichia coli. Biotechnol. Bioeng. 117, 2139–2152 (2020).

    Article  CAS  PubMed  Google Scholar 

  54. Zhao, P., Ma, C., Xu, L. & Tian, P. Exploiting tandem repetitive promoters for high-level production of 3-hydroxypropionic acid. Appl. Microbiol. Biotechnol. 103, 4017–4031 (2019).

    Article  PubMed  Google Scholar 

  55. Jakobblinnert, A. & Rother, D. A two-step biocatalytic cascade in microaqueous medium: using whole cells to obtain high concentrations of a vicinal diol. Green Chem. 16, 3472–3482 (2014).

    Article  Google Scholar 

  56. Scholz, K. E. et al. Synthesis of chiral cyanohydrins by recombinant Escherichia coli cells in a microaqueous reaction system. Appl. Environ. Microbiol. 78, 5025–5027 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yarkent, Ç & Öncel, S. S. Recent progress in microalgal squalene production and its cosmetic application. Biotechnol. Bioprocess Eng. 27, 295–305 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Plass, C. et al. Approaching bulk chemical nitriles from alkenes: a hydrogen cyanide-free approach through a combination of hydroformylation and biocatalysis. ACS Catal. 9, 5198–5203 (2019).

    Article  CAS  Google Scholar 

  59. Hernik, D. et al. Chemo-enzymatic synthesis and biological activity evaluation of propenylbenzene derivatives. Front. Microbiol. 14, 1005654 (2023).

    Article  Google Scholar 

  60. Willke, T. & Vorlop, K. D. Biotechnological production of itaconic acid. Appl. Microbiol. Biotechnol. 56, 289–295 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Werpy, T. & Petersen, G. Top Value-Added Chemicals from Biomass: Volume I—Results of Screening for Potential Candidates from Sugars and Synthesis Gas Report No. ORNL/TM 2004 (US DOE, 2004).

  62. Shemesh, M. et al. Light-driven and bias-free direct conversion of cellulose to electrical power. Cell Rep. Phys. Sci. 4, 101546 (2023).

    Article  CAS  Google Scholar 

  63. Milton, R. D. et al. Bioelectrochemical Haber–Bosch process: an ammonia-producing H2/N2 fuel cell. Angew. Chem. Int. Ed. Engl. 56, 2680–2683 (2017).

    Article  CAS  PubMed  Google Scholar 

  64. Meirovich, M. M. et al. Light-driven, bias-free nitrogenase-based bioelectrochemical cell for ammonia generation. Biosens. Bioelectron. 255, 116254 (2024).

    Article  Google Scholar 

  65. Castañeda Losada, L. et al. Bioelectrocatalytic cofactor regeneration coupled to CO2 fixation in a redox-active hydrogel for stereoselective C–C bond formation. Angew. Chem. Int. Ed. Engl. 60, 21056–21061 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Wang, H. & Ren, Z. J. A comprehensive review of microbial electrochemical systems as a platform technology. Biotechnol. Adv. 31, 1796–1807 (2013).

    Article  PubMed  Google Scholar 

  67. Bajracharya, S. et al. An overview on emerging bioelectrochemical systems (BESs): technology for sustainable electricity, waste remediation, resource recovery, chemical production and beyond. Renew. Energy 98, 153–170 (2016).

    Article  CAS  Google Scholar 

  68. Cheng, S. & Logan, B. E. Sustainable and efficient biohydrogen production via electrohydrogenesis. Proc. Natl Acad. Sci. USA 104, 18871–18873 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jack, J., Zhu, W., Avalos, J. L., Gong, J. & Ren, Z. J. Anode co-valorization for scalable and sustainable electrolysis. Green Chem. 23, 7917–7936 (2021).

    Article  CAS  Google Scholar 

  70. Kracke, F., Vassilev, I. & Krömer, J. O. Microbial electron transport and energy conservation—the foundation for optimizing bioelectrochemical systems. Front. Microbiol. 6, 575 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Shi, L. et al. Extracellular electron transfer mechanisms between microorganisms and minerals. Nat. Rev. Microbiol. 14, 651–661 (2016).

    Article  CAS  PubMed  Google Scholar 

  72. Li, Y. et al. Biological self-assembled transmembrane electron conduits for high-efficiency ammonia production in microbial electrosynthesis. Environ. Sci. Technol. 58, 7457–7468 (2024). By enhancing EET, this study addresses a major bottleneck in microbial electrosynthesis and demonstrates efficient ammonia production.

    Article  CAS  PubMed  Google Scholar 

  73. Erisman, J. W., Sutton, M. A., Galloway, J., Klimont, Z. & Winiwarter, W. How a century of ammonia synthesis changed the world. Nat. Geosci. 1, 636–639 (2008).

    Article  CAS  Google Scholar 

  74. Shi, H. et al. Engineered Escherichia coli whole-cell mediated electro-biocatalysis for carbon dioxide to formic acid conversion. ACS Sustain. Chem. Eng. 12, 5544–5554 (2024).

    Article  CAS  Google Scholar 

  75. Cai, W. et al. An electrolytic hydrogen-fed moving-bed biofilm reactor for efficient microbial electrosynthesis of methane from CO2. Chem. Eng. J. 428, 132093 (2022).

    Article  CAS  Google Scholar 

  76. Liu, G. et al. Biosynthetic CdS–Thiobacillus thioparus hybrid for solar-driven carbon dioxide fixation. Nano Res. 16, 4531–4538 (2023).

    Article  CAS  Google Scholar 

  77. Guo, J. et al. Light-driven fine chemical production in yeast biohybrids. Science 362, 813–816 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Malihan-Yap, L. et al. Light-driven photobiocatalytic oxyfunctionalization in a continuous reactor system without external oxygen supply. ACS Sustain. Chem. Eng. 13, 3939–3950 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Shen, J., Liu, Y. & Qiao, L. Photodriven chemical synthesis by whole-cell-based biohybrid systems: from system construction to mechanism study. ACS Appl. Mater. Interfaces 15, 6235–6259 (2023).

    Article  CAS  PubMed  Google Scholar 

  80. Ji, Z., Zhang, H., Liu, H., Yaghi, O. M. & Yang, P. Cytoprotective metal–organic frameworks for anaerobic bacteria. Proc. Natl Acad. Sci. USA 115, 10582–10587 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Dasuri, K., Zhang, L. & Keller, J. N. Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis. Free Radic. Biol. Med. 62, 170–185 (2013).

    Article  CAS  PubMed  Google Scholar 

  82. Sakimoto, K. K., Wong, A. B. & Yang, P. Self-photosensitization of nonphotosynthetic bacteria for solar to chemical production. Science 351, 74–77 (2016).

    Article  CAS  PubMed  Google Scholar 

  83. Bachar, O., Meirovich, M. M., Zeibaq, Y. & Yehezkeli, O. Protein-mediated biosynthesis of semiconductor nanocrystals for photocatalytic NAD(P)H regeneration and chiral amine production. Angew. Chem. Int. Ed. Engl. 61, e202212345 (2022).

    Article  Google Scholar 

  84. Spangler, L. C. et al. A de novo protein catalyzes the synthesis of semiconductor quantum dots. Proc. Natl Acad. Sci. USA 119, e2210273119 (2022).

    Article  Google Scholar 

  85. Wang, Y. et al. Effect and mechanism of simultaneous cadmium/tetracycline removal by a self-assembled microbial photocatalytic coupling system. J. Hazard. Mater. 449, 131018 (2023).

    Article  CAS  PubMed  Google Scholar 

  86. Liu, K. et al. Enhanced degradation of azo dyes wastewater by S-scheme heterojunction photocatalyst g-C3N4/MoS2 intimately coupled with Rhodopseudomonas palustris on a chitosan-modified polyurethane sponge carrier. Int. J. Hydrog. Energy 48, 22319–22333 (2023).

    Article  CAS  Google Scholar 

  87. Liu, Q. et al. Integrated photocatalysis and moving bed biofilm reactor (MBBR) for treating conventional and emerging organic pollutants from synthetic wastewater: performances and microbial community responses. Bioresour. Technol. 370, 128530 (2023).

    Article  CAS  PubMed  Google Scholar 

  88. Yu, W. et al. Solar-driven production of value-added chemicals with an organic semiconductor-bacteria biohybrid system. Research 2022, 8031542 (2022).

    Article  Google Scholar 

  89. Eriksen, D. T., HamediRad, M., Yuan, Y. & Zhao, H. Orthogonal fatty acid biosynthetic pathway improves fatty acid ethyl ester production in Saccharomyces cerevisiae. ACS Synth. Biol. 4, 808–814 (2015).

    Article  CAS  PubMed  Google Scholar 

  90. Rinaldi, M. A., Ferraz, C. A. & Scrutton, N. S. Alternative metabolic pathways and strategies to high-titre terpenoid production in Escherichia coli. Nat. Prod. Rep. 39, 90–118 (2022).

    Article  CAS  PubMed  Google Scholar 

  91. Kong, X. et al. Efficient synthesis of limonene in Saccharomyces cerevisiae using combinatorial metabolic engineering strategies. J. Agric. Food Chem. 71, 7752–7764 (2023).

    Article  CAS  PubMed  Google Scholar 

  92. Siripong, W. et al. Metabolic engineering of Pichia pastoris for production of isobutanol and isobutyl acetate. Biotechnol. Biofuels 11, 1 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Milne, N. et al. Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives. Metab. Eng. 60, 25–36 (2020). This landmark work demonstrates complete de novo microbial production of a complex neuroactive compound from glucose, laying groundwork for biosynthetic pharmaceuticals.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Chen, H. et al. High-yield porphyrin production through metabolic engineering and biocatalysis. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02267-3 (2024). This study illustrates industrial-scale production of porphyrins through a hybrid biological–enzymatic process, supported by technoeconomic validation.

  95. Philipps, G., de Vries, S. & Jennewein, S. Development of a metabolic pathway transfer and genomic integration system for the syngas-fermenting bacterium Clostridium ljungdahlii. Biotechnol. Biofuels 12, 112 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Liu, Y. et al. An in vitro hybrid biocatalytic system enabled by a combination of surface-displayed, purified, and cell-free expressed enzymes. ACS Synth. Biol. 13, 1434–1441 (2024).

    Article  CAS  PubMed  Google Scholar 

  97. Black, W. B. et al. Engineering a nicotinamide mononucleotide redox cofactor system for biocatalysis. Nat. Chem. Biol. 16, 87–94 (2020).

    Article  CAS  PubMed  Google Scholar 

  98. Weng, C., Peng, X. & Han, Y. Depolymerization and conversion of lignin to value-added bioproducts by microbial and enzymatic catalysis. Biotechnol. Biofuels Bioprod. 17, 2 (2024).

    Google Scholar 

  99. Salvachúa, D. et al. Lignin depolymerization by fungal secretomes and a microbial sink. Green Chem. 18, 6046–6062 (2016).

    Article  Google Scholar 

  100. Gu, J. et al. Bacterial transformation of lignin: key enzymes and high-value products. Biotechnol. Biofuels Bioprod. 17, 2 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the Swiss National Science Foundation for financial support (grant number 200021-232199). This publication is also part of NCCR Catalysis (grant number 225147), a National Centre of Competence in Research funded by the Swiss National Science Foundation.

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  1. These authors contributed equally: Stefania Gianolio, Arpita Mrigwani.

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  1. Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland

    Stefania Gianolio, Arpita Mrigwani & Francesca Paradisi

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Gianolio, S., Mrigwani, A. & Paradisi, F. Advances in integrating microbial metabolism with catalytic systems. Nat Chem Biol (2025). https://doi.org/10.1038/s41589-025-02048-2

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