1. Schmitz, L.M.; Rosenthal, K.; Lütz, S. Recent Advances in Heme Biocatalysis Engineering. Biotechnol. Bioeng. 2019, 116, 3469-3475. [CrossRef] [PubMed]

2. Isin, E.M.; Guengerich, F.P. Complex Reactions Catalyzed by Cytochrome P450 Enzymes. Biochim. Biophys. Acta 2007, 1770, 314- 329. [CrossRef] [PubMed]

3. Hanefeld, U.; Hollmann, F.; Paul, C.E. Biocatalysis Making Waves in Organic Chemistry. Chem. Soc. Rev. 2022, 51, 594-627. [CrossRef] [PubMed]

4. Lamb, D.C.; Waterman, M.R. Unusual Properties of the Cytochrome P450 Superfamily. Philos. Trans. R. Soc. B Biol. Sci. 2013, 368, 20120434. [CrossRef]

Int. J. Mol. Sci. 2023, 24, 214 17 of 21

5. Meng, S.; Ji, Y.; Zhu, L.; Dhoke, G.V.; Davari, M.D.; Schwaneberg, U. The Molecular Basis and Enzyme Engineering Strategies for Improvement of Coupling Efficiency in Cytochrome P450s. Biotechnol. Adv. 2022, 61, 108051. [CrossRef] [PubMed]

6. Xu, J.; Wang, C.; Cong, Z. Strategies for Substrate-Regulated P450 Catalysis: From Substrate Engineering to Co-Catalysis. Chem. Eur. J. 2019, 25, 6853-6863. [CrossRef] [PubMed]

7. Stanfield, J.K.; Shoji, O. The Power of Deception: Using Decoy Molecules to Manipulate P450BM3 Biotransformations. Chem. Lett. 2021, 50, 2025-2031. [CrossRef]

8. Shoji, O.; Fujishiro, T.; Nishio, K.; Kano, Y.; Kimoto, H.; Chien, S.; Onoda, H.; Muramatsu, A.; Tanaka, S.; Hori, A.; et al. A Substrate-Binding-State Mimic of H2 O2 -Dependent Cytochrome P450 Produced by One-point Mutagenesis and Peroxygenation of Non-native Substrates. Catal. Sci. Technol. 2016, 6, 5806-5811. [CrossRef]

9. Hobisch, M.; Holtmann, D.; Gomez de Santos, P.; Alcalde, M.; Hollmann, F.; Kara, S. Recent Developments in the Use of Peroxygenases—Exploring Their High Potential in Selective Oxyfunctionalisations. Biotechnol. Adv. 2021, 51, 107615. [CrossRef]

10. Chen, Z.; Ost, T.W.B.; Schelvis, J.P.M. Phe393 Mutants of Cytochrome P450 BM3 with Modified Heme Redox Potentials Have Altered Heme Vinyl and Propionate Conformations. Biochemistry 2004, 43, 1798-1808. [CrossRef]

11. Guengerich, F.P.; Munro, A.W. Unusual Cytochrome P450 Enzymes and Reactions. J. Biol. Chem. 2013, 288, 17065-17073. [CrossRef] [PubMed]

12. Wuttke, D.S.; Gray, H.B. Protein Engineering as a Tool for Understanding Electron Transfer: Current Opinion in Structural Biology 1993, 3:555-563. Curr. Opin. Struct. Biol. 1993, 3, 555-563. [CrossRef]

13. Sono, M.; Roach, M.P.; Coulter, E.D.; Dawson, J.H. Heme-Containing Oxygenases. Chem. Rev. 1996, 96, 2841-2888. [CrossRef] [PubMed]

14. Auclair, K.; Moënne-Loccoz, P.; Ortiz de Montellano, P.R. Roles of the Proximal Heme Thiolate Ligand in Cytochrome P450(Cam). J. Am. Chem. Soc. 2001, 123, 4877-4885. [CrossRef] [PubMed]

15. Reedy, C.J.; Elvekrog, M.M.; Gibney, B.R. Development of a Heme Protein Structure-Electrochemical Function Database. Nucleic Acids Res. 2008, 36, D307-D313. [CrossRef]

16. Vatsis, K.P.; Peng, H.-M.; Coon, M.J. Replacement of Active-Site Cysteine-436 by Serine Converts Cytochrome P450 2B4 into an NADPH Oxidase with Negligible Monooxygenase Activity. J. Inorg. Biochem. 2002, 91, 542-553. [CrossRef]

17. Coelho, P.S.; Wang, Z.J.; Ener, M.E.; Baril, S.A.; Kannan, A.; Arnold, F.H.; Brustad, E.M. A Serine-Substituted P450 Catalyzes Highly Efficient Carbene Transfer to Olefins in Vivo. Nat. Chem. Biol. 2013, 9, 485-487. [CrossRef]

18. Ariyasu, S.; Stanfield, J.K.; Aiba, Y.; Shoji, O. Expanding the Applicability of Cytochrome P450s and Other Haemoproteins. Curr. Opin. Chem. Biol. 2020, 59, 155-163. [CrossRef]

19. Shoji, O.; Watanabe, Y. Monooxygenation of Small Hydrocarbons Catalyzed by Bacterial Cytochrome P450s. Adv. Exp. Med. Biol. 2015, 851, 189-208. [CrossRef]

20. Ost, T.W.; Miles, C.S.; Munro, A.W.; Murdoch, J.; Reid, G.A.; Chapman, S.K. Phenylalanine 393 Exerts Thermodynamic Control over the Heme of Flavocytochrome P450 BM3. Biochemistry 2001, 40, 13421-13429. [CrossRef]

21. Daiber, A.; Nauser, T.; Takaya, N.; Kudo, T.; Weber, P.; Hultschig, C.; Shoun, H.; Ullrich, V. Isotope Effects and Intermediates in the Reduction of NO by P450(NOR). J. Inorg. Biochem. 2002, 88, 343-352. [CrossRef] [PubMed]

22. de Visser, S.P.; Ogliaro, F.; Sharma, P.K.; Shaik, S. What Factors Affect the Regioselectivity of Oxidation by Cytochrome P450? A DFT Study of Allylic Hydroxylation and Double Bond Epoxidation in a Model Reaction. J. Am. Chem. Soc. 2002, 124, 11809-11826. [CrossRef] [PubMed]

23. Adachi, S.; Nagano, S.; Ishimori, K.; Watanabe, Y.; Morishima, I.; Egawa, T.; Kitagawa, T.; Makino, R. Roles of Proximal Ligand in Heme Proteins: Replacement of Proximal Histidine of Human Myoglobin with Cysteine and Tyrosine by Site-Directed Mutagenesis as Models for P-450, Chloroperoxidase, and Catalase. Biochemistry 1993, 32, 241-252. [CrossRef] [PubMed]

24. Liu, Y.; Moënne-Loccoz, P.; Hildebrand, D.P.; Wilks, A.; Loehr, T.M.; Mauk, A.G.; Ortiz de Montellano, P.R. Replacement of the Proximal Histidine Iron Ligand by a Cysteine or Tyrosine Converts Heme Oxygenase to an Oxidase. Biochemistry 1999, 38, 3733-3743. [CrossRef]

25. Ogliaro, F.; de Visser, S.P.; Shaik, S. The “push” Effect of the Thiolate Ligand in Cytochrome P450: A Theoretical Gauging. J. Inorg. Biochem. 2002, 91, 554-567. [CrossRef]

26. Lang, J.; Santolini, J.; Couture, M. The Conserved Trp-Cys Hydrogen Bond Dampens the “Push Effect” of the Heme Cysteinate Proximal Ligand during the First Catalytic Cycle of Nitric Oxide Synthase. Biochemistry 2011, 50, 10069-10081. [CrossRef]

27. Davydov, R.; Im, S.; Shanmugam, M.; Gunderson, W.A.; Pearl, N.M.; Hoffman, B.M.; Waskell, L. Role of the Proximal Cysteine Hydrogen Bonding Interaction in Cytochrome P450 2B4 Studied by Cryoreduction, Electron Paramagnetic Resonance, and Electron-Nuclear Double Resonance Spectroscopy. Biochemistry 2016, 55, 869-883. [CrossRef]

28. Yoshioka, S.; Tosha, T.; Takahashi, S.; Ishimori, K.; Hori, H.; Morishima, I. Roles of the Proximal Hydrogen Bonding Network in Cytochrome P450cam-Catalyzed Oxygenation. J. Am. Chem. Soc. 2002, 124, 14571-14579. [CrossRef]

29. Cupp-Vickery, J.R.; Poulos, T.L. Structure of Cytochrome P450eryF Involved in Erythromycin Biosynthesis. Nat. Struct. Mol. Biol. 1995, 2, 144-153. [CrossRef]

30. Ravichandran, K.G.; Boddupalli, S.S.; Hasermann, C.A.; Peterson, J.A.; Deisenhofer, J. Crystal Structure of Hemoprotein Domain of P450BM-3, a Prototype for Microsomal P450's. Science 1993, 261, 731-736. [CrossRef]

Int. J. Mol. Sci. 2023, 24, 214 18 of 21

31. Boddupalli, S.S.; Hasemann, C.A.; Ravichandran, K.G.; Lu, J.Y.; Goldsmith, E.J.; Deisenhofer, J.; Peterson, J.A. Crystallization and Preliminary X-ray Diffraction Analysis of P450terp and the Hemoprotein Domain of P450BM-3, Enzymes Belonging to Two Distinct Classes of the Cytochrome P450 Superfamily. Proc. Natl. Acad. Sci. USA 1992, 89, 5567-5571. [CrossRef] [PubMed]

32. Sundaramoorthy, M.; Terner, J.; Poulos, T.L. The Crystal Structure of Chloroperoxidase: A Heme Peroxidase-Cytochrome P450 Functional Hybrid. Structure 1995, 3, 1367-1377. [CrossRef] [PubMed]

33. Crane, B.R.; Arvai, A.S.; Gachhui, R.; Wu, C.; Ghosh, D.K.; Getzoff, E.D.; Stuehr, D.J.; Tainer, J.A. The Structure of Nitric Oxide Synthase Oxygenase Domain and Inhibitor Complexes. Science 1997, 278, 425-431. [CrossRef] [PubMed]

34. Ueno, T.; Nishikawa, N.; Moriyama, S.; Adachi, S.; Lee, K.; Okamura Ta, T.; Ueyama, N.; Nakamura, A. Role of the Invariant Peptide Fragment Forming NH.S Hydrogen Bonds in the Active Site of Cytochrome P-450 and Chloroperoxidase: Synthesis and Properties of Cys-Containing Peptide Fe(III) and Ga(III) (Octaethylporphinato) Complexes as Models. Inorg. Chem. 1999, 38, 1199-1210. [CrossRef] [PubMed]

35. Suzuki, N.; Higuchi, T.; Urano, Y.; Kikuchi, K.; Uekusa, H.; Ohashi, Y.; Uchida, T.; Kitagawa, T.; Nagano, T. Novel Iron PorphyrinAlkanethiolate Complex with Intramolecular NH···S Hydrogen Bond: Synthesis, Spectroscopy, and Reactivity. J. Am. Chem. Soc. 1999, 121, 11571-11572. [CrossRef]

36. Davies, H.M.L.; Manning, J.R. Catalytic C-H Functionalization by Metal Carbenoid and Nitrenoid Insertion. Nature 2008, 451, 417-424. [CrossRef]

37. Liu, Y.; Xiao, W.; Wong, M.-K.; Che, C.-M. Transition-Metal-Catalyzed Group Transfer Reactions for Selective C-H Bond Functionalization of Artemisinin. Org. Lett. 2007, 9, 4107-4110. [CrossRef]

38. van Vliet, K.M.; de Bruin, B. Dioxazolones: Stable Substrates for the Catalytic Transfer of Acyl Nitrenes. ACS Catal. 2020, 10, 4751-4769. [CrossRef]

39. Coelho, P.S.; Brustad, E.M.; Kannan, A.; Arnold, F.H. Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes. Science 2013, 339, 307-310. [CrossRef]

40. Dydio, P.; Key, H.M.; Hayashi, H.; Clark, D.S.; Hartwig, J.F. Chemoselective, Enzymatic C-H Bond Amination Catalyzed by a Cytochrome P450 Containing an Ir(Me)-PIX Cofactor. J. Am. Chem. Soc. 2017, 139, 1750-1753. [CrossRef]

41. Chen, K.; Zhang, S.-Q.; Brandenberg, O.F.; Hong, X.; Arnold, F.H. Alternate Heme Ligation Steers Activity and Selectivity in Engineered Cytochrome P450-Catalyzed Carbene-Transfer Reactions. J. Am. Chem. Soc. 2018, 140, 16402-16407. [CrossRef] [PubMed]

42. Liu, Z.; Arnold, F.H. New-to-Nature Chemistry from Old Protein Machinery: Carbene and Nitrene Transferases. Curr. Opin. Biotechnol. 2021, 69, 43-51. [CrossRef] [PubMed]

43. Kreß, N.; Halder, J.M.; Rapp, L.R.; Hauer, B. Unlocked Potential of Dynamic Elements in Protein Structures: Channels and Loops. Curr. Opin. Chem. Biol. 2018, 47, 109-116. [CrossRef] [PubMed]

44. Di Nardo, G.; Gilardi, G. Natural Compounds as Pharmaceuticals: The Key Role of Cytochromes P450 Reactivity. Trends Biochem. Sci. 2020, 45, 511-525. [CrossRef]

45. Aleku, G.A.; France, S.P.; Man, H.; Mangas-Sanchez, J.; Montgomery, S.L.; Sharma, M.; Leipold, F.; Hussain, S.; Grogan, G.; Turner, N.J. A Reductive Aminase from Aspergillus Oryzae. Nat. Chem. 2017, 9, 961-969. [CrossRef]

46. Man, H.; Wells, E.; Hussain, S.; Leipold, F.; Hart, S.; Turkenburg, J.P.; Turner, N.J.; Grogan, G. Structure, Activity and Stereoselec tivity of NADPH-Dependent Oxidoreductases Catalysing the S-Selective Reduction of the Imine Substrate 2-Methylpyrroline. Chembiochem 2015, 16, 1052-1059. [CrossRef]

47. Wetzl, D.; Berrera, M.; Sandon, N.; Fishlock, D.; Ebeling, M.; Müller, M.; Hanlon, S.; Wirz, B.; Iding, H. Expanding the Imine Reductase Toolbox by Exploring the Bacterial Protein-Sequence Space. Chembiochem 2015, 16, 1749-1756. [CrossRef]

48. Aleku, G.A.; Man, H.; France, S.P.; Leipold, F.; Hussain, S.; Toca-Gonzalez, L.; Marchington, R.; Hart, S.; Turkenburg, J.P.; Grogan, G.; et al. Stereoselectivity and Structural Characterization of an Imine Reductase (IRED) from Amycolatopsis orientalis. ACS Catal. 2016, 6, 3880-3889. [CrossRef]

49. Grogan, G. Synthesis of chiral amines using redox biocatalysis. Curr. Opin. Chem. Biol. 2017, 43, 15-22. [CrossRef]

50. Wang, J.-B.; Li, G.; Reetz, M.T. Enzymatic site-selectivity enabled by structure-guided directed evolution. Chem. Commun. 2017, 53, 3916-3928. [CrossRef]

51. Schober, M.; Faber, K. Inverting Hydrolases and Their Use in Enantioconvergent Biotransformations. Trends Biotechnol. 2013, 31, 468-478. [CrossRef] [PubMed]

52. Wijma, H.J.; Floor, R.J.; Bjelic, S.; Marrink, S.J.; Baker, D.; Janssen, D.B. Enantioselective Enzymes by Computational Design and In Silico Screening. Angew. Chem. Int. Ed. 2015, 54, 3726-3730. [CrossRef] [PubMed]

53. Xu, G.-C.; Wang, Y.; Tang, M.-H.; Zhou, J.-Y.; Zhao, J.; Han, R.-Z.; Ni, Y. Hydroclassified Combinatorial Saturation Mutagenesis: Reshaping Substrate Binding Pockets of KpADH for Enantioselective Reduction of Bulky-Bulky Ketones. ACS Catal. 2018, 8, 8336-8345. [CrossRef]

54. Li, R.; Wijma, H.; Song, L.; Cui, Y.-L.; Otzen, M.; Tian, Y.; Du, J.; Li, T.; Niu, D.; Chen, Y.; et al. Computational redesign of enzymes for regioand enantioselective hydroamination. Nat. Chem. Biol. 2018, 14, 664-670. [CrossRef]

55. Shen, Z.; Lv, C.; Zeng, S. Significance and Challenges of Stereoselectivity Assessing Methods in Drug Metabolism. J. Pharm. Anal. 2016, 6, 1-10. [CrossRef] [PubMed]

56. Singh, R.; Kolev, J.N.; Sutera, P.A.; Fasan, R. Enzymatic C(Sp3)-H Amination: P450-Catalyzed Conversion of Carbonazidates into Oxazolidinones. ACS Catal. 2015, 5, 1685-1691. [CrossRef]

Int. J. Mol. Sci. 2023, 24, 214 19 of 21

57. Singh, R.; Bordeaux, M.; Fasan, R. P450-Catalyzed Intramolecular sp 3 C-H Amination with Arylsulfonyl Azide Substrates. ACS Catal. 2014, 4, 546-552. [CrossRef]

58. McIntosh, J.A.; Coelho, P.S.; Farwell, C.C.; Wang, Z.J.; Lewis, J.C.; Brown, T.R.; Arnold, F.H. Enantioselective Intramolecular C-H Amination Catalyzed by Engineered Cytochrome P450 Enzymes in Vitro and in Vivo. Angew. Chem. Int. Ed. 2013, 52, 9309-9312. [CrossRef]

59. Farwell, C.C.; McIntosh, J.A.; Hyster, T.K.; Wang, Z.J.; Arnold, F.H. Enantioselective Imidation of Sulfides via Enzyme-Catalyzed Intermolecular Nitrogen-Atom Transfer. J. Am. Chem. Soc. 2014, 136, 8766-8771. [CrossRef]

60. Farwell, C.C.; Zhang, R.K.; McIntosh, J.A.; Hyster, T.K.; Arnold, F.H. Enantioselective Enzyme-Catalyzed Aziridination Enabled by Active-Site Evolution of a Cytochrome P450. ACS Cent. Sci. 2015, 1, 89-93. [CrossRef]

61. Prier, C.K.; Zhang, R.K.; Buller, A.R.; Brinkmann-Chen, S.; Arnold, F.H. Enantioselective, Intermolecular Benzylic C-H Amination Catalysed by an Engineered Iron-Haem Enzyme. Nat. Chem. 2017, 9, 629-634. [CrossRef]

62. Hyster, T.K.; Arnold, F.H. P450BM3-Axial Mutations: A Gateway to Non-Natural Reactivity. Isr. J. Chem. 2015, 55, 14-20. [CrossRef]

63. Prier, C.K.; Hyster, T.K.; Farwell, C.C.; Huang, A.; Arnold, F.H. Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy. Angew. Chem. Int. Ed. 2016, 55, 4711-4715. [CrossRef] [PubMed]

64. Sreenilayam, G.; Fasan, R. Myoglobin-Catalyzed Intermolecular Carbene N-H Insertion with Arylamine Substrates. Chem. Commun. 2015, 51, 1532-1534. [CrossRef] [PubMed]

65. Tyagi, V.; Bonn, R.B.; Fasan, R. Intermolecular Carbene S-H Insertion Catalysed by Engineered Myoglobin-Based Catalysts. Chem. Sci. 2015, 6, 2488-2494. [CrossRef]

66. Giovani, S.; Singh, R.; Fasan, R. Efficient conversion of primary azides to aldehydes catalyzed by active site variants of myoglobin. Chem. Sci. 2015, 7, 234-239. [CrossRef]

67. Tyagi, V.; Fasan, R. Myoglobin-Catalyzed Olefination of Aldehydes. Angew. Chem. Int. Ed. 2016, 55, 2512-2516. [CrossRef]

68. Tyagi, V.; Sreenilayam, G.; Bajaj, P.; Tinoco, A.; Fasan, R. Biocatalytic Synthesis of Allylic and Allenyl Sulfides through a Myoglobin-Catalyzed Doyle-Kirmse Reaction. Angew. Chem. Int. Ed. 2016, 55, 13562-13566. [CrossRef]

69. Tinoco, A.; Steck, V.; Tyagi, V.; Fasan, R. Highly Diastereoand Enantioselective Synthesis of Trifluoromethyl-Substituted Cyclopropanes via Myoglobin-Catalyzed Transfer of Trifluoromethylcarbene. J. Am. Chem. Soc. 2017, 139, 5293-5296. [CrossRef]

70. Bajaj, P.; Sreenilayam, G.; Tyagi, V.; Fasan, R. Gram-Scale Synthesis of Chiral Cyclopropane-Containing Drugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity. Angew. Chem. Int. Ed. 2016, 55, 16110-16114. [CrossRef]

71. Oohora, K.; Kihira, Y.; Mizohata, E.; Inoue, T.; Hayashi, T. C(Sp3)-H Bond Hydroxylation Catalyzed by Myoglobin Reconstituted with Manganese Porphycene. J. Am. Chem. Soc. 2013, 135, 17282-17285. [CrossRef] [PubMed]

72. Hayashi, T.; Murata, D.; Makino, M.; Sugimoto, H.; Matsuo, T.; Sato, H.; Shiro, Y.; Hisaeda, Y. Crystal Structure and Peroxidase Activity of Myoglobin Reconstituted with Iron Porphycene. Inorg. Chem. 2006, 45, 10530-10536. [CrossRef] [PubMed]

73. Oohora, K.; Meichin, H.; Kihira, Y.; Sugimoto, H.; Shiro, Y.; Hayashi, T. Manganese(V) Porphycene Complex Responsible for Inert C-H Bond Hydroxylation in a Myoglobin Matrix. J. Am. Chem. Soc. 2017, 139, 18460-18463. [CrossRef] [PubMed]

74. Cai, Y.-B.; Li, X.-H.; Jing, J.; Zhang, J.-L. Effect of distal histidines on hydrogen peroxide activation by manganese reconstituted myoglobin. Metallomics 2013, 5, 828-835. [CrossRef]

75. Shoji, O.; Watanabe, Y. Design of H2 O2 -Dependent Oxidation Catalyzed by Hemoproteins. Metallomics 2011, 3, 379-388. [CrossRef] [PubMed]

76. Hayashi, T.; Hisaeda, Y. New Functionalization of Myoglobin by Chemical Modification of Heme-Propionates. Acc. Chem. Res. 2002, 35, 35-43. [CrossRef] [PubMed]

77. Markel, U.; Sauer, D.F.; Wittwer, M.; Schiffels, J.; Cui, H.; Davari, M.D.; Kröckert, K.W.; Herres-Pawlis, S.; Okuda, J.; Schwaneberg, U. Chemogenetic Evolution of a Peroxidase-like Artificial Metalloenzyme. ACS Catal. 2021, 11, 5079-5087. [CrossRef]

78. Davis, H.J.; Ward, T.R. Artificial Metalloenzymes: Challenges and Opportunities. ACS Cent. Sci. 2019, 5, 1120-1136. [CrossRef]

79. Maity, B.; Taher, M.; Mazumdar, S.; Ueno, T. Artificial Metalloenzymes Based on Protein Assembly. Coord. Chem. Rev. 2022, 469, 214593. [CrossRef]

80. Zhou, Q.; Chin, M.; Fu, Y.; Liu, P.; Yang, Y. Stereodivergent Atom-Transfer Radical Cyclization by Engineered Cytochromes P450. Science 2021, 374, 1612-1616. [CrossRef]

81. Hauk, G.; McKnight, J.N.; Nodelman, I.M.; Bowman, G.D. The Chromodomains of the Chd1 Chromatin Remodeler Regulate DNA Access to the ATPase Motor. Mol. Cell 2010, 39, 711-723. [CrossRef] [PubMed]

82. Turberville, A.; Semple, H.; Davies, G.; Ivanov, D.; Holdgate, G.A. A Perspective on the Discovery of Enzyme Activators. SLAS Discov. 2022, 27, 419-427. [CrossRef] [PubMed]

83. Teng, M.; Young, D.W.; Tan, Z. The Pursuit of Enzyme Activation: A Snapshot of the Gold Rush. J. Med. Chem. 2022, 65, 14289-14304. [CrossRef]

84. Dai, Y.; Lin, J.; Ren, J.; Zhu, B.; Wu, C.; Yu, L. NAD+ Metabolism in Peripheral Neuropathic Pain. Neurochem. Int. 2022, 161, 105435. [CrossRef]

85. Matsunaga, I.; Ueda, A.; Fujiwara, N.; Sumimoto, T.; Ichihara, K. Characterization of the YbdT Gene Product of Bacillus Subtilis: Novel Fatty Acid Beta-Hydroxylating Cytochrome P450. Lipids 1999, 34, 841-846. [CrossRef] [PubMed]

Int. J. Mol. Sci. 2023, 24, 214 20 of 21

86. Lee, D.-S.; Yamada, A.; Sugimoto, H.; Matsunaga, I.; Ogura, H.; Ichihara, K.; Adachi, S.-I.; Park, S.-Y.; Shiro, Y. Substrate Recognition and Molecular Mechanism of Fatty Acid Hydroxylation by Cytochrome P450 from Bacillus subtilis. Crystallographic, Spectroscopic, and Mutational Studies. J. Biol. Chem. 2003, 278, 9761-9767. [CrossRef] [PubMed]

87. Shoji, O.; Fujishiro, T.; Nakajima, H.; Kim, M.; Nagano, S.; Shiro, Y.; Watanabe, Y. Hydrogen Peroxide Dependent Monooxy genations by Tricking the Substrate Recognition of Cytochrome P450BSbeta. Angew. Chem. Int. Ed. 2007, 46, 3656-3659. [CrossRef]

88. Shoji, O.; Watanabe, Y. Bringing out the Potential of Wild-Type Cytochrome P450s Using Decoy Molecules: Oxygenation of Nonnative Substrates by Bacterial Cytochrome P450s. Isr. J. Chem. 2015, 55, 32-39. [CrossRef]

89. Kawakami, N.; Shoji, O.; Watanabe, Y. Use of Perfluorocarboxylic Acids to Trick Cytochrome P450BM3 into Initiating the Hydroxylation of Gaseous Alkanes. Angew. Chem. Int. Ed. 2011, 50, 5315-5318. [CrossRef]

90. Shoji, O.; Kunimatsu, T.; Kawakami, N.; Watanabe, Y. Highly Selective Hydroxylation of Benzene to Phenol by Wild-type Cytochrome P450BM3 Assisted by Decoy Molecules. Angew. Chem. Int. Ed. 2013, 52, 6606-6610. [CrossRef]

91. Zilly, F.E.; Acevedo, J.P.; Augustyniak, W.; Deege, A.; Häusig, U.W.; Reetz, M.T. Tuning a P450 Enzyme for Methane Oxidation. Angew. Chem. Int. Ed. 2011, 50, 2720-2724. [CrossRef] [PubMed]

92. Onoda, H.; Shoji, O.; Watanabe, Y. Acetate Anion-Triggered Peroxygenation of Non-Native Substrates by Wild-Type Cytochrome P450s. Dalton Trans. 2015, 44, 15316-15323. [CrossRef] [PubMed]

93. Shoji, O.; Wiese, C.; Fujishiro, T.; Shirataki, C.; Wünsch, B.; Watanabe, Y. Aromatic C-H bond hydroxylation by P450 peroxygenases: A facile colorimetric assay for monooxygenation activities of enzymes based on Russig's blue formation. JBIC J. Biol. Inorg. Chem. 2010, 15, 1109-1115. [CrossRef]

94. Fujishiro, T.; Shoji, O.; Kawakami, N.; Watanabe, T.; Sugimoto, H.; Shiro, Y.; Watanabe, Y. Chiral-Substrate-Assisted Stereoselective Epoxidation Catalyzed by H2 O2 -Dependent Cytochrome P450SPα. Chem. Asian J. 2012, 7, 2286-2293. [CrossRef]

95. Suzuki, K.; Stanfield, J.K.; Shoji, O.; Yanagisawa, S.; Sugimoto, H.; Shiro, Y.; Watanabe, Y. Control of Stereoselectivity of Benzylic Hydroxylation Catalysed by Wild-Type Cytochrome P450BM3 Using Decoy Molecules. Catal. Sci. Technol. 2017, 7, 3332-3338. [CrossRef]

96. Whitehouse, C.J.C.; Bell, S.G.; Wong, L.-L. P450(BM3) (CYP102A1): Connecting the Dots. Chem. Soc. Rev. 2012, 41, 1218-1260. [CrossRef]

97. Shoji, O.; Yanagisawa, S.; Stanfield, J.K.; Suzuki, K.; Cong, Z.; Sugimoto, H.; Shiro, Y.; Watanabe, Y. Direct Hydroxylation of Benzene to Phenol by Cytochrome P450BM3 Triggered by Amino Acid Derivatives. Angew. Chem. Int. Ed. 2017, 56, 10324-10329. [CrossRef]

98. Dezvarei, S.; Lee, J.H.Z.; Bell, S.G. Stereoselective Hydroxylation of Isophorone by Variants of the Cytochromes P450 CYP102A1 and CYP101A1. Enzym. Microb. Technol. 2018, 111, 29-37. [CrossRef]

99. Ma, N.; Chen, Z.; Chen, J.; Chen, J.; Wang, C.; Zhou, H.; Yao, L.; Shoji, O.; Watanabe, Y.; Cong, Z. Dual-Functional Small Molecules for Generating an Efficient Cytochrome P450BM3 Peroxygenase. Angew. Chem. Int. Ed. 2018, 57, 7628-7633. [CrossRef]

100. Ma, N.; Fang, W.; Liu, C.; Qin, X.; Wang, X.; Jin, L.; Wang, B.; Cong, Z. Switching an Artificial P450 Peroxygenase into Peroxidase via Mechanism-Guided Protein Engineering. ACS Catal. 2021, 11, 8449-8455. [CrossRef]

101. Zhao, P.; Chen, J.; Ma, N.; Chen, J.; Qin, X.; Liu, C.; Yao, F.; Yao, L.; Jin, L.; Cong, Z. Enabling Highly (R)-Enantioselective Epoxidation of Styrene by Engineering Unique Non-Natural P450 Peroxygenases. Chem. Sci. 2021, 12, 6307-6314. [CrossRef]

102. Li, M.; Miao, H.; Li, Y.; Wang, F.; Xu, J. Protein Engineering of an Artificial P450BM3 Peroxygenase System Enables Highly Selective O-Demethylation of Lignin Monomers. Molecules 2022, 27, 3120. [CrossRef]

103. Lundemo, M.T.; Woodley, J.M. Guidelines for Development and Implementation of Biocatalytic P450 Processes. Appl. Microbiol. Biotechnol. 2015, 99, 2465-2483. [CrossRef]

104. Podgorski, M.N.; Harbort, J.S.; Lee, J.H.Z.; Nguyen, G.T.; Bruning, J.B.; Donald, W.A.; Bernhardt, P.V.; Harmer, J.R.; Bell, S.G. An Altered Heme Environment in an Engineered Cytochrome P450 Enzyme Enables the Switch from Monooxygenase to Peroxygenase Activity. ACS Catal. 2022, 12, 1614-1625. [CrossRef]

105. Bornscheuer, U.T.; Hauer, B.; Jaeger, K.E.; Schwaneberg, U. Directed Evolution Empowered Redesign of Natural Proteins for the Sustainable Production of Chemicals and Pharmaceuticals. Angew. Chem. Int. Ed. 2019, 58, 36-40. [CrossRef]

106. Abdelraheem, E.M.; Busch, H.; Hanefeld, U.; Tonin, F. Biocatalysis Explained: From Pharmaceutical to Bulk Chemical Production. React. Chem. Eng. 2019, 4, 1878-1894. [CrossRef]

107. Rajakumara, E.; Abhishek, S.; Nitin, K.; Saniya, D.; Bajaj, P.; Schwaneberg, U.; Davari, M.D. Structure and Cooperativity in Substrate-Enzyme Interactions: Perspectives on Enzyme Engineering and Inhibitor Design. ACS Chem. Biol. 2022, 17, 266-280. [CrossRef]

108. Yang, Y.; Arnold, F.H. Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for Selective Carbene and Nitrene Transfer. Acc. Chem. Res. 2021, 54, 1209-1225. [CrossRef]

109. Wang, X.; Pereira, J.H.; Tsutakawa, S.; Fang, X.; Adams, P.D.; Mukhopadhyay, A.; Lee, T.S. Efficient Production of Oxidized Terpenoids via Engineering Fusion Proteins of Terpene Synthase and Cytochrome P450. Metab. Eng. 2021, 64, 41-51. [CrossRef]

110. Saroay, R.; Roiban, G.-D.; Alkhalaf, L.M.; Challis, G.L. Expanding the Substrate Scope of Nitrating Cytochrome P450 TxtE by Active Site Engineering of a Reductase Fusion. ChemBioChem 2021, 22, 2262-2265. [CrossRef]

Int. J. Mol. Sci. 2023, 24, 214 21 of 21

111. Ellis, E.S.; Hinchen, D.J.; Bleem, A.; Bu, L.; Mallinson, S.J.B.; Allen, M.D.; Streit, B.R.; Machovina, M.M.; Doolin, Q.V.; Michener, W.E.; et al. Engineering a Cytochrome P450 for Demethylation of Lignin-Derived Aromatic Aldehydes. JACS Au 2021, 1, 252-261. [CrossRef] [PubMed]

112. Park, H.; Bak, D.; Jeon, W.; Jang, M.; Ahn, J.-O.; Choi, K.-Y. Engineering of CYP153A33 with Enhanced Ratio of Hydroxylation to Overoxidation Activity in Whole-Cell Biotransformation of Medium-Chain 1-Alkanols. Front. Bioeng. Biotechnol. 2022, 9, 817455. [CrossRef] [PubMed]

113. Urlacher, V.B.; Girhard, M. Cytochrome P450 Monooxygenases in Biotechnology and Synthetic Biology. Trends Biotechnol. 2019, 37, 882-897. [CrossRef] [PubMed]

114. Zhang, L.; Wang, Q. Harnessing P450 Enzyme for Biotechnology and Synthetic Biology. Chembiochem 2022, 23, e202100439. [CrossRef] [PubMed]

Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual

author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to

people or property resulting from any ideas, methods, instructions or products referred to in the content.