Fig. 15 Directed evolution enhances the fluorination activity of non-heme iron oxidase^[108-109]

Fig. 1 Halogens are the most common and important modification groups in pesticides and pharmaceutical products
Fig. 2 Examples of halogenated natural products and the role of halogenases in molecular synthesis^[4,12,15-16]
Fig. 3 Cofactors and catalytic mechanisms of different types of halogenase^[1,4,17-25]
Fig. 4 Workflow of genome mining for halogenases and their application examples^[34]
Table 1 Examples of halogenase discovered by genome mining
Table 2 The uniqueness and superiority of the CLEAN algorithm framework
Fig. 5 Overview of chloride depletion workflow for revealing cryptic halogenation^[59]
Fig. 6 The typical structure and catalytic elements of flavin-dependent halogenases
Fig. 7 The typical structure of single-component flavin-dependent halogenases
Fig. 8 The proposed catalytic mechanism of PrnA by calculation and simulation^[69]
Fig. 9 The typical structure of NHFe/αKGHs^[25,70-76]
Fig. 10 The proposed catalytic mechanism of BesD by calculation and simulation^[80]
Fig. 11 The action mode and engineering strategies of novel nucleotide halogenase ^[46]
Fig.12 The structural, function and catalytic mechanism of copper-dependent halogenase ApnU^[81]
Table 3 Typical engineering cases of natural halogenase in recent years
Fig. 13 The typical structure SAM-dependent halogenase^[84-91]The red lines indicate the residues that are crucial for fluorination activity; the yellow lines indicate the residues that can form hydrogen bonds with the modification groups at the C2′ position of adenine
Fig. 14 Tunnel engineering improves the catalytic performance of Thal halogenase^[96]
Fig. 16 Biocatalytic synthesis platform of halogenated tryptophan derivatives^[113]
Tab. 4 Examples of FDHs catalyzing enantioselective reactions^[125-127]
Tab. 5 Recent cases and key data related to the potential industrial application of halogenases
Fig. 17 Representative research progress in the field of halogenase research
Fig. 18 AI/ML drives the intelligent evolution of halogenase^[138-156]