Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

RetroBioCat as a computer-aided synthesis planning tool for biocatalytic reactions and cascades

Abstract

As the enzyme toolbox for biocatalysis has expanded, so has the potential for the construction of powerful enzymatic cascades for efficient and selective synthesis of target molecules. Additionally, recent advances in computer-aided synthesis planning are revolutionizing synthesis design in both synthetic biology and organic chemistry. However, the potential for biocatalysis is not well captured by tools currently available in either field. Here we present RetroBioCat, an intuitive and accessible tool for computer-aided design of biocatalytic cascades, freely available at retrobiocat.com. Our approach uses a set of expertly encoded reaction rules encompassing the enzyme toolbox for biocatalysis, and a system for identifying literature precedent for enzymes with the correct substrate specificity where this is available. Applying these rules for automated biocatalytic retrosynthesis, we show our tool to be capable of identifying promising biocatalytic pathways to target molecules, validated using a test set of recent cascades described in the literature.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: An overview of the requirements for a biocatalysis CASP tool.
Fig. 2: Critical components of RetroBioCat.
Fig. 3: Human-led exploration of a network of potential biotransformations using network explorer.
Fig. 4: An example selection of some of the biocatalytic cascades identified in the literature and used as a test set for pathway explorer.

Data availability

Other than literature precedent data, which can currently only be accessed at https://retrobiocat.com pending future publications, the database files for RetroBiocat at the time of publication are available at https://doi.org/10.6084/m9.figshare.12696482.v4. The 52 pathway test set is available, along with the source code at https://doi.org/10.6084/m9.figshare.12698072.v7 or https://github.com/willfinnigan/retrobiocat.

Code availability

RetroBioCat is freely available as a web application at https://retrobiocat.com. We have also made the source code freely available under the MIT license, available at https://github.com/willfinnigan/retrobiocat, or specifically for the version described here, at https://doi.org/10.6084/m9.figshare.12698072.v7.

References

  1. 1.

    Bornscheuer, U. T. et al. Engineering the third wave of biocatalysis. Nature 485, 185–194 (2012).

    CAS  PubMed  Google Scholar 

  2. 2.

    Sheldon, R. A. & Brady, D. The limits to biocatalysis: pushing the envelope. Chem. Commun. 54, 6088–6104 (2018).

    CAS  Google Scholar 

  3. 3.

    Hönig, M., Sondermann, P., Turner, N. J. & Carreira, E. M. Enantioselective chemo- and biocatalysis: partners in retrosynthesis. Angew. Chem. Int. Ed. Engl. 56, 8942–8973 (2017).

    PubMed  Google Scholar 

  4. 4.

    France, S. P., Hepworth, L. J., Turner, N. J. & Flitsch, S. L. Constructing biocatalytic cascades: in vitro and in vivo approaches to de novo multi-enzyme pathways. ACS Catal. 7, 710–724 (2017).

    CAS  Google Scholar 

  5. 5.

    Huffman, M. A. et al. Design of an in vitro biocatalytic cascade for the manufacture of islatravir. Science 366, 1255–1259 (2019).

    CAS  PubMed  Google Scholar 

  6. 6.

    Schober, M. et al. Chiral synthesis of LSD1 inhibitor GSK2879552 enabled by directed evolution of an imine reductase. Nat. Catal. 2, 909–915 (2019).

    CAS  Google Scholar 

  7. 7.

    Koch, M., Duigou, T. & Faulon, J. L. Reinforcement learning for bioretrosynthesis. ACS Synth. Biol. 9, 157–168 (2020).

    CAS  PubMed  Google Scholar 

  8. 8.

    Coley, C. W., Rogers, L., Green, W. H. & Jensen, K. F. Computer-assisted retrosynthesis based on molecular similarity. ACS Cent. Sci. 3, 1237–1245 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Szymkuć, S. et al. Computer-assisted synthetic planning: the end of the beginning. Angew. Chem. Int. Ed. Engl. 55, 5904–5937 (2016).

    PubMed  Google Scholar 

  10. 10.

    Segler, M. H. S., Preuss, M. & Waller, M. P. Planning chemical syntheses with deep neural networks and symbolic AI. Nature 555, 604–610 (2018).

    CAS  PubMed  Google Scholar 

  11. 11.

    Landrum, G. RDKit: open-cource cheminformatics software (2016).

  12. 12.

    Coley, C. W., Green, W. H. & Jensen, K. F. Machine learning in computer-aided synthesis planning. Acc. Chem. Res. 51, 1281–1289 (2018).

    CAS  PubMed  Google Scholar 

  13. 13.

    Grzybowski, B. A. et al. Chematica: a story of computer code that started to think like a chemist. Chem 4, 390–398 (2018).

    CAS  Google Scholar 

  14. 14.

    Hartenfeller, M. et al. A collection of robust organic synthesis reactions for in silico molecule design. J. Chem. Inf. Model. 51, 3093–3098 (2011).

    CAS  PubMed  Google Scholar 

  15. 15.

    Plehiers, P. P., Marin, G. B., Stevens, C. V. & Van Geem, K. M. Automated reaction database and reaction network analysis: extraction of reaction templates using cheminformatics. J. Cheminform. 10, 11 (2018).

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Duigou, T., Du Lac, M., Carbonell, P. & Faulon, J. L. Retrorules: a database of reaction rules for engineering biology. Nucleic Acids Res. 47, D1229–D1235 (2019).

    PubMed  Google Scholar 

  17. 17.

    Molga, K., Gajewska, E. P., Szymkuć, S. & Grzybowski, B. A. The logic of translating chemical knowledge into machine-processable forms: a modern playground for physical-organic chemistry. React. Chem. Eng. 4, 1506–1521 (2019).

    CAS  Google Scholar 

  18. 18.

    Segler, M. H. S. & Waller, M. P. Neural-symbolic machine learning for retrosynthesis and reaction prediction. Chem. Eur. J. 23, 5966–5971 (2017).

    CAS  PubMed  Google Scholar 

  19. 19.

    Fehér, T. et al. Validation of RetroPath, a computer-aided design tool for metabolic pathway engineering. Biotechnol. J. 9, 1446–1457 (2014).

    PubMed  Google Scholar 

  20. 20.

    Turner, N. J. & Humphreys, L. Biocatalysis in Organic Synthesis: the Retrosynthesis Approach (Royal Society of Chemistry, 2018).

  21. 21.

    Turner, N. J. & O’Reilly, E. Biocatalytic retrosynthesis. Nat. Chem. Biol. 9, 285–288 (2013).

    CAS  PubMed  Google Scholar 

  22. 22.

    de Souza, R. O. M. A., Miranda, L. S. M. & Bornscheuer, U. T. A retrosynthesis approach for biocatalysis in organic synthesis. Chem. Eur. J. 23, 12040–12063 (2017).

    PubMed  Google Scholar 

  23. 23.

    Heath, R. S. et al. An engineered alcohol oxidase for the oxidation of primary alcohols. ChemBioChem 20, 276–281 (2019).

    CAS  PubMed  Google Scholar 

  24. 24.

    Batista, V. F., Galman, J. L., Pinto, D. C., Silva, A. M. S. & Turner, N. J. Monoamine oxidase: tunable activity for amine resolution and functionalization. ACS Catal. 8, 11889–11907 (2018).

    CAS  Google Scholar 

  25. 25.

    Devine, P. N. et al. Extending the application of biocatalysis to meet the challenges of drug development. Nat. Rev. Chem. 2, 409–421 (2018).

    Google Scholar 

  26. 26.

    Arnold, F. H. Directed evolution: bringing new chemistry to life. Angew. Chem. Int. Ed. Engl. 57, 4143–4148 (2018).

    CAS  PubMed  Google Scholar 

  27. 27.

    Rácz, A., Bajusz, D. & Héberger, K. Life beyond the Tanimoto coefficient: similarity measures for interaction fingerprints. J. Cheminform. 10, 1–12 (2018).

    Google Scholar 

  28. 28.

    Breitling, R. et al. Selenzyme: enzyme selection tool for pathway design. Bioinformatics 34, 2153–2154 (2018).

    PubMed  Google Scholar 

  29. 29.

    Coley, C. W., Rogers, L., Green, W. H. & Jensen, K. F. SCScore: synthetic complexity learned from a reaction corpus. J. Chem. Inf. Model. 58, 252–261 (2018).

    CAS  PubMed  Google Scholar 

  30. 30.

    Genheden, S. et al. AiZynthFinder: a fast, robust and flexible open-source software for retrosynthetic planning. J Cheminform. 12, 70 (2020).

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Sehl, T. et al. Two steps in one pot: enzyme cascade for the synthesis of nor(pseudo)ephedrine from inexpensive starting materials. Angew. Chem. Int. Ed. Engl. 52, 6772–6775 (2013).

    CAS  PubMed  Google Scholar 

  32. 32.

    Wang, J. et al. Efficient production of phenylpropionic acids by an amino-group-transformation biocatalytic cascade. Biotechnol. Bioeng. 117, 614–625 (2020).

    CAS  PubMed  Google Scholar 

  33. 33.

    Erdmann, V. et al. Methoxamine synthesis in a biocatalytic 1-pot 2-step cascade approach. ACS Catal. 9, 7380–7388 (2019).

    CAS  Google Scholar 

  34. 34.

    Lichman, B. R. et al. One-pot triangular chemoenzymatic cascades for the syntheses of chiral alkaloids from dopamine. Green Chem. 17, 852–855 (2015).

    CAS  Google Scholar 

  35. 35.

    Parmeggiani, F., Lovelock, S. L., Weise, N. J., Ahmed, S. T. & Turner, N. J. Synthesis of d- and l-phenylalanine derivatives by phenylalanine ammonia lyases: a multienzymatic cascade process. Angew. Chem. Int. Ed. Engl. 54, 4608–4611 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Both, P. et al. Whole-cell biocatalysts for stereoselective C-H amination reactions. Angew. Chem. Int. Ed. Engl. 55, 1511–1513 (2016).

    CAS  PubMed  Google Scholar 

  37. 37.

    Oberleitner, N. et al. From waste to value—direct utilization of limonene from orange peel in a biocatalytic cascade reaction towards chiral carvolactone. Green Chem. 19, 367–371 (2017).

    CAS  Google Scholar 

  38. 38.

    Wu, S. et al. Highly regio- and enantioselective multiple oxy- and amino-functionalizations of alkenes by modular cascade biocatalysis. Nat. Commun. 7, 11917 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Ramsden, J. I. et al. Biocatalytic N-alkylation of amines using either primary alcohols or carboxylic acids via reductive aminase cascades. J. Am. Chem. Soc. 141, 1201–1206 (2019).

    CAS  PubMed  Google Scholar 

  40. 40.

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

    CAS  Google Scholar 

  41. 41.

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Busto, E., Simon, R. C. & Kroutil, W. Vinylation of unprotected phenols using a biocatalytic system. Angew. Chem. Int. Ed. Engl. 54, 10899–10902 (2015).

    CAS  PubMed  Google Scholar 

  43. 43.

    Citoler, J., Derrington, S. R., Galman, J. L., Bevinakatti, H. & Turner, N. J. A biocatalytic cascade for the conversion of fatty acids to fatty amines. Green Chem. 21, 4932–4935 (2019).

    CAS  Google Scholar 

  44. 44.

    Thorpe, T. W. et al. One-pot biocatalytic cascade reduction of cyclic enimines for the preparation of diastereomerically enriched N-heterocycles. J. Am. Chem. Soc. 141, 19208–19213 (2019).

    CAS  PubMed  Google Scholar 

  45. 45.

    Heath, R. S., Pontini, M., Hussain, S. & Turner, N. J. Combined imine reductase and amine oxidase catalyzed deracemization of nitrogen heterocycles. ChemCatChem 8, 117–120 (2016).

    CAS  Google Scholar 

  46. 46.

    Tavanti, M., Mangas-Sanchez, J., Montgomery, S. L., Thompson, M. P. & Turner, N. J. A biocatalytic cascade for the amination of unfunctionalised cycloalkanes. Org. Biomol. Chem. 15, 9790–9793 (2017).

    CAS  PubMed  Google Scholar 

  47. 47.

    Sattler, J. H. et al. Redox self-sufficient biocatalyst network for the amination of primary alcohols. Angew. Chem. Int. Ed. Engl. 51, 9156–9159 (2012).

    CAS  PubMed  Google Scholar 

  48. 48.

    Mourelle-Insua, Á., Zampieri, L. A., Lavandera, I. & Gotor-Fernández, V. Conversion of γ- and δ-keto esters into optically active lactams. Transaminases in cascade processes. Adv. Synth. Catal. 360, 686–695 (2018).

    CAS  Google Scholar 

  49. 49.

    Aumala, V. et al. Biocatalytic production of amino carbohydrates through oxidoreductase and transaminase cascades. ChemSusChem 12, 848–857 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Song, J.-W. et al. Multistep enzymatic synthesis of long-chain α,ω-dicarboxylic and ω-hydroxycarboxylic acids from renewable fatty acids and plant oils. Angew. Chem. Int. Ed. Engl. 52, 2534–2537 (2013).

    CAS  PubMed  Google Scholar 

  51. 51.

    Corrado, M. L., Knaus, T. & Mutti, F. G. Regio- and stereoselective multi-enzymatic aminohydroxylation of β-methylstyrene using dioxygen, ammonia and formate. Green Chem. 21, 6246–6251 (2019).

    CAS  Google Scholar 

  52. 52.

    Fedorchuk, T. P. et al. One-pot biocatalytic transformation of adipic acid to 6-aminocaproic acid and 1,6-hexamethylenediamine using carboxylic acid reductases and transaminases. J. Am. Chem. Soc. 142, 1038–1048 (2020).

    CAS  PubMed  Google Scholar 

  53. 53.

    Wang, H., Zheng, Y.-C., Chen, F.-F., Xu, J.-H. & Yu, H.-L. Enantioselective bioamination of aromatic alkanes using ammonia: a multienzymatic cascade approach. ChemCatChem 12, 2077–2082 (2020).

    CAS  Google Scholar 

  54. 54.

    Pickl, M., Fuchs, M., Glueck, S. M. & Faber, K. Amination of ω-functionalized aliphatic primary alcohols by a biocatalytic oxidation-transamination cascade. ChemCatChem 7, 3121–3124 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Parmeggiani, F. et al. One-pot biocatalytic synthesis of substituted d-tryptophans from indoles enabled by an engineered aminotransferase. ACS Catal. 9, 3482–3486 (2019).

    CAS  Google Scholar 

  56. 56.

    Zhang, Z.-J., Cai, R.-F. & Xu, J.-H. Characterization of a new nitrilase from Hoeflea phototrophica DFL-43 for a two-step one-pot synthesis of (S)-β-amino acids. Appl. Microbiol. Biotechnol. 102, 6047–6056 (2018).

    CAS  PubMed  Google Scholar 

  57. 57.

    Bechi, B. et al. Catalytic bio-chemo and bio-bio tandem oxidation reactions for amide and carboxylic acid synthesis. Green Chem. 16, 4524–4529 (2014).

    CAS  Google Scholar 

  58. 58.

    Jia, H.-Y., Zong, M.-H., Zheng, G.-W. & Li, N. One-pot enzyme cascade for controlled synthesis of furancarboxylic acids from 5-hydroxymethylfurfural by H2O2 internal recycling. ChemSusChem 12, 4764–4768 (2019).

    CAS  PubMed  Google Scholar 

  59. 59.

    Alvarenga, N. et al. Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to Krapcho dealkoxycarbonylation. ACS Catal. 10, 1607–1620 (2020).

    CAS  Google Scholar 

  60. 60.

    Weise, N. J. et al. Bi-enzymatic conversion of cinnamic acids to 2-arylethylamines. ChemCatChem 12, 995–998 (2020).

    CAS  Google Scholar 

  61. 61.

    Yoon, S. et al. Deracemization of racemic amines to enantiopure (R)- and (S)-amines by biocatalytic cascade employing ω-transaminase and amine dehydrogenase. ChemCatChem 11, 1898–1902 (2019).

    CAS  Google Scholar 

  62. 62.

    Steinreiber, J. et al. Overcoming thermodynamic and kinetic limitations of aldolase-catalyzed reactions by applying multienzymatic dynamic kinetic asymmetric transformations. Angew. Chem. Int. Ed. Engl. 46, 1624–1626 (2007).

    CAS  PubMed  Google Scholar 

  63. 63.

    Shanmuganathan, S., Natalia, D., Greiner, L. & Domínguez de María, P. Oxidation-hydroxymethylation-reduction: a one-pot three-step biocatalytic synthesis of optically active α-aryl vicinal diols. Green Chem. 14, 94–97 (2012).

    CAS  Google Scholar 

  64. 64.

    Montgomery, S. L. et al. Direct alkylation of amines with primary and secondary alcohols through biocatalytic hydrogen borrowing. Angew. Chem. Int. Ed. Engl. 129, 10627–10630 (2017).

    Google Scholar 

  65. 65.

    Guérard-Hélaine, C. et al. Stereoselective synthesis of γ-hydroxy-α-amino acids through aldolase-transaminase recycling cascades. Chem. Commun. 53, 5465–5468 (2017).

    Google Scholar 

  66. 66.

    Siirola, E. et al. Asymmetric synthesis of 3-substituted cyclohexylamine derivatives from prochiral diketones via three biocatalytic steps. Adv. Synth. Catal. 355, 1703–1708 (2013).

    CAS  Google Scholar 

  67. 67.

    Zhang, J.-D. et al. Asymmetric ring opening of racemic epoxides for enantioselective synthesis of (S)-β-amino alcohols by a cofactor self-sufficient cascade biocatalysis system. Catal. Sci. Technol. 9, 70–74 (2019).

    CAS  Google Scholar 

  68. 68.

    France, S. P. et al. One-pot cascade synthesis of mono- and disubstituted piperidines and pyrrolidines using carboxylic acid reductase (CAR), ω-transaminase (ω-TA), and imine reductase (IRED) biocatalysts. ACS Catal. 6, 3753–3759 (2016).

    CAS  Google Scholar 

  69. 69.

    Hernandez, K. et al. Combining aldolases and transaminases for the synthesis of 2-amino-4-hydroxybutanoic acid. ACS Catal. 7, 1707–1711 (2017).

    CAS  Google Scholar 

  70. 70.

    Monti, D. et al. Cascade coupling of ene-reductases and ω-transaminases for the stereoselective synthesis of diastereomerically enriched amines. ChemCatChem 7, 3106–3109 (2015).

    CAS  Google Scholar 

  71. 71.

    Liao, C. & Seebeck, F. P. Asymmetric β-methylation of l- and d-α-amino acids by a self-contained enzyme cascade. Angew. Chem. Int. Ed. Engl. 59, 7184–7187 (2020).

    CAS  PubMed  Google Scholar 

  72. 72.

    Schmidt, S. et al. Biocatalytic access to chiral polyesters by an artificial enzyme cascade synthesis. ChemCatChem 7, 3951–3955 (2015).

    CAS  Google Scholar 

  73. 73.

    Li, X. et al. DeepChemStable: chemical stability prediction with an attention-based graph convolution network. J. Chem. Inf. Model. 59, 1044–1049 (2019).

    CAS  PubMed  Google Scholar 

  74. 74.

    Finnigan, W. et al. Engineering a seven enzyme biotransformation using mathematical modelling and characterized enzyme parts. ChemCatChem 11, 3474–3489 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Chen, B., Li, C., Dai, H. & Song, L. Retro*: learning retrosynthetic planning with neural guided A* search. Preprint at https://arxiv.org/abs/2006.15820 (2020).

  76. 76.

    Kishimoto, A., Buesser, B., Chen, B. & Botea, A. in Advances in Neural Information Processing Systems (eds Wallach, H. et al.) 7226–7236 (Curran Associates, 2019).

  77. 77.

    Coley, C. W., Green, W. H. & Jensen, K. F. RDChiral: an RDKit wrapper for handling stereochemistry in retrosynthetic template extraction and application. J. Chem. Inf. Model. 59, 2529–2537 (2019).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge financial support from the European Research Council (788231-ProgrES-ERC-2017-ADG to S.L.F.; BIO-HBORROW: grant no. 742987 to N.J.T.). We also thank all the beta-testers of RetroBioCat, particularly S. Cosgrove and R. Speight.

Author information

Affiliations

Authors

Contributions

W.F., L.J.H., S.L.F. and N.J.T. planned the work. Code for RetroBioCat written by W.F. Pathway test set generated by L.J.H. Initial draft of the manuscript written by W.F., with subsequent contributions from L.J.H., S.L.F. and N.J.T. All authors have given approval to the final version of the manuscript.

Corresponding authors

Correspondence to Sabine L. Flitsch or Nicholas J. Turner.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Catalysis thanks Connor Coley, Nicolas Moitessier, Dörte Rother and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 An example generated using Network Explorer to illustrate changes in molecular complexity.

Arrows and reactions are coloured by the change in molecular complexity, determined using the SC-Score. Green indicates a negative change in molecule complexity, which in most cases corresponds to a synthetically useful transformation. Red indicates a positive change in molecular complexity. Colours are determined relative to the other transformations leading to a specific molecule. Some reactions have been removed for clarity. Pathway published in reference68.

Extended Data Fig. 2 Rankings for pathways 12 to 20 of the test-set for Pathway explorer.

A continuation of Fig. 4, showing rankings for pathways 12 to 20 by RetroBioCat using a maximum of 4 steps and either the default scoring weights, or default weights but with the weight for number of steps with literature precedent set to zero, are shown. Pathways are marked as identified even where RetroBioCat suggests additional steps. * indicates pathways where the data from the relevant paper has not been added to the database of literature precedent reactions in RetroBioCat. TPL: tyrosine phenol lyase, AAD: amino acid deaminase, AADH: amino acid dehydrogenase, TDL: thiamine-dependent lyase, TA: transaminase, PSase: Pictet-Spenglerase, PAL: phenylalanine ammonia lyase, P450: cytochrome P450, ADH: alcohol dehydrogenase, CumDO: cumene dioxygenase, ERED: ene reductase, BVMO: Baeyer-Villiger monooxygenase, SMO: styrene monooxygenase, AlDH: aldehyde dehydrogenase, AlOx: alcohol oxidase.

Extended Data Fig. 3 Rankings for pathways 21 to 30 of the test-set for Pathway explorer.

A continuation of Fig. 4, showing rankings for pathways 21 to 30 by RetroBioCat using a maximum of 4 steps and either the default scoring weights, or default weights but with the weight for number of steps with literature precedent set to zero, are shown. Pathways are marked as identified even where RetroBioCat suggests additional steps. * indicates pathways where the data from the relevant paper has not been added to the database of literature precedent reactions in RetroBioCat. TDL: thiamine-dependent lyase, ADH: alcohol dehydrogenase, PAL: phenylalanine ammonia lyase, CAR: carboxylic acid reductase, ERED: ene reductase, IRED: imine reductase, AmOx: amine oxidase, P450: cytochrome P450, ATP: adenosine triphosphate, NADP: nicotinamide adenine dinucleotide phosphate.

Extended Data Fig. 4 Rankings for pathways 31 to 40 of the test-set for Pathway explorer.

A continuation of Fig. 4, showing rankings for pathways 31 to 40 by RetroBioCat using a maximum of 4 steps and either the default scoring weights, or default weights but with the weight for number of steps with literature precedent set to zero, are shown. Pathways are marked as identified even where RetroBioCat suggests additional steps. * indicates pathways where the data from the relevant paper has not been added to the database of literature precedent reactions in RetroBioCat. ADH: alcohol dehydrogenase, BVMO: Baeyer-Villiger monooxygenase, SMO: styrene monooxygenase, EH: epoxide hydrolase, AmDH: amine dehydrogenase, CAR: carboxylic acid reductase, TA: transaminase, AlOx: alcohol oxidase, ERED: ene reductase, TrpS: tryptophan synthase, XOR: xanthine oxidoreductase, AAD: amino acid deaminase, ATP: adenosine triphosphate, NADP: nicotinamide adenine dinucleotide phosphate, BNA: 1-benzyl-1,4-dihydropyridine-3-carboxamide.

Extended Data Fig. 5 Rankings for pathways 41 to 52 of the test-set for Pathway explorer.

A continuation of Fig. 4, showing rankings for pathways 41 to 52 by RetroBioCat using a maximum of 4 steps and either the default scoring weights, or default weights but with the weight for number of steps with literature precedent set to zero, are shown. Pathways are marked as identified even where RetroBioCat suggests additional steps. * indicates pathways where the data from the relevant paper has not been added to the database of literature precedent reactions in RetroBioCat. TA: transaminase, IRED: imine reductase, PAL: phenylalanine ammonia lyase, DC: decarboxylase, AmDH: amine dehydrogenase, TPL: tyrosine phenol lyase, AAD: amino acid deaminase, TAM: tyrosine aminomutase, TDL: thiamine-dependent lyase, ADH: alcohol dehydrogenase, AlOx: alcohol oxidase, EH: epoxide hydrolase, CAR: carboxylic acid reductase, ATP: adenosine triphosphate, NADP: nicotinamide adenine dinucleotide phosphate.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Finnigan, W., Hepworth, L.J., Flitsch, S.L. et al. RetroBioCat as a computer-aided synthesis planning tool for biocatalytic reactions and cascades. Nat Catal 4, 98–104 (2021). https://doi.org/10.1038/s41929-020-00556-z

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing