{
    "accession": "MITE0000419",
    "status": "active",
    "comment": "Halogenation of the coupled aglycone containing ring A and B in the clorobiocin pathway. Bromine has higher affinity to CloHal but yields less bromobiocin due to lower turnover rate. Iodination and fluorination not possible ",
    "changelog": [
        {
            "version": "1",
            "date": "2026-07-13",
            "contributors": [
                "0009-0000-8651-1669"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "New entry."
        }
    ],
    "enzyme": {
        "name": "CloHal",
        "description": "Flavin-dependent halogenase",
        "references": [
            "doi:10.1128/spectrum.00423-24",
            "doi:10.1016/S1074-5521(03)00051-6"
        ],
        "databaseIds": {
            "uniprot": "Q8GHB4",
            "genpept": "AAN65237.1",
            "mibig": "BGC0000832"
        },
        "cofactors": {
            "organic": [
                "FAD"
            ]
        }
    },
    "reactions": [
        {
            "tailoring": [
                "Halogenation"
            ],
            "description": "Chlorination of ring B of the aglycone intermediate",
            "reactionSMARTS": "[#6:1]1(-[#8:28]):[#6:6]:[#6:5]:[#6:4]2:[#6:7](-[#8:27]):[#6:8](-[#7:12]-[#6:13](-[#6:15]3:[#6:20]:[#6:19]:[#6:18](-[#8:21]):[#6:17](-[#6:22]-[#6:23]=[#6:24](-[#6:26])-[#6:25]):[#6:16]:3)=[#8:14]):[#6:9](:[#8:11]:[#6:3]:2:[#6:2]:1)=[#8:10]>>[#6:1]1(-[#8:28]):[#6:6]:[#6:5]:[#6:4]2:[#6:7](-[#8:27]):[#6:8](-[#7:12]-[#6:13](-[#6:15]3:[#6:20]:[#6:19]:[#6:18](-[#8:21]):[#6:17](-[#6:22]-[#6:23]=[#6:24](-[#6:25])-[#6:26]):[#6:16]:3)=[#8:14]):[#6:9](:[#8:11]:[#6:3]:2:[#6:2]:1-[Cl])=[#8:10]",
            "reactions": [
                {
                    "substrate": "CC(C)=CCc1cc(C(=O)Nc2c(O)c3ccc(O)cc3oc2=O)ccc1O",
                    "products": [
                        "CC(C)=CCc1cc(C(=O)Nc2c(O)c3ccc(O)c(Cl)c3oc2=O)ccc1O"
                    ],
                    "isIntermediate": true,
                    "description": "C-8 chlorination of the aminocoumarin moiety"
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "Heterologous expression",
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1128/spectrum.00423-24"
                ]
            }
        },
        {
            "tailoring": [
                "Halogenation"
            ],
            "description": "Bromination of ring B of the aglycone intermediate",
            "reactionSMARTS": "[#6:1]1(-[#8:28]):[#6:6]:[#6:5]:[#6:4]2:[#6:7](-[#8:27]):[#6:8](-[#7:12]-[#6:13](-[#6:15]3:[#6:20]:[#6:19]:[#6:18](-[#8:21]):[#6:17](-[#6:22]-[#6:23]=[#6:24](-[#6:26])-[#6:25]):[#6:16]:3)=[#8:14]):[#6:9](:[#8:11]:[#6:3]:2:[#6:2]:1)=[#8:10]>>[#6:1]1(-[#8:28]):[#6:6]:[#6:5]:[#6:4]2:[#6:7](-[#8:27]):[#6:8](-[#7:12]-[#6:13](-[#6:15]3:[#6:20]:[#6:19]:[#6:18](-[#8:21]):[#6:17](-[#6:22]-[#6:23]=[#6:24](-[#6:25])-[#6:26]):[#6:16]:3)=[#8:14]):[#6:9](:[#8:11]:[#6:3]:2:[#6:2]:1-Br)=[#8:10]",
            "reactions": [
                {
                    "substrate": "CC(C)=CCc1cc(C(=O)Nc2c(O)c3ccc(O)cc3oc2=O)ccc1O",
                    "products": [
                        "CC(C)=CCc1cc(C(=O)Nc2c(O)c3ccc(O)c(Br)c3oc2=O)ccc1O"
                    ],
                    "isIntermediate": true,
                    "description": "C-8 bromination of the aminocoumarin moiety"
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "Heterologous expression",
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1128/spectrum.00423-24"
                ]
            }
        }
    ]
}