{
    "accession": "MITE0000273",
    "status": "active",
    "comment": "FAD-dependent halogenase responsible for bromination of W1 of darobactin A, yielding bromo-darobactin. Represents a new class of flavin-dependent halogenases with a novel fold, co-purified with FAD.",
    "changelog": [
        {
            "version": "1",
            "date": "2026-03-30",
            "contributors": [
                "AAAAAAAAAAAAAAAAAAAAAAAA"
            ],
            "reviewers": [
                "0000-0002-9747-3423"
            ],
            "comment": "New entry."
        },
        {
            "version": "2",
            "date": "2026-07-05",
            "contributors": [
                "AAAAAAAAAAAAAAAAAAAAAAAA"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "Replaced retired UniProt ID with UniParc ID."
        }
    ],
    "enzyme": {
        "name": "DarH",
        "description": "Halogenase",
        "references": [
            "doi:10.1016/j.chembiol.2023.06.011"
        ],
        "databaseIds": {
            "uniprot": "UPI0007B0A84C",
            "genpept": "KZN44487.1"
        },
        "cofactors": {
            "organic": [
                "FAD"
            ]
        }
    },
    "reactions": [
        {
            "tailoring": [
                "Halogenation"
            ],
            "description": "Bromination of C-8 of W1 of darobactin A, yielding bromodarobactin A.",
            "reactionSMARTS": "[#8:1]=[#6:2]1-[#7:22]-[#6:17](-[#6:18]-[#6:19](-[#7:21])=[#8:20])-[#6:15](=[#8:16])-[#7:14]-[#6:13]2-[#6:23](-[#7:25]-[#6:26](-[#6:29](-[#7:31]-[#6:32](-[#6:53](-[#6:58]3:[#6:63]:[#6:62]:[#6:61]4:[#6:64](:[#6:65]:[#7:66]:[#6:60]:4:[#6:59]:3)-[#6:12]-2-[#8:11]-[#6:10]2:[#6:67]3:[#7:68]:[#6:69]:[#6:5](:[#6:6]:3:[#6:7]:[#6:8]:[#6:9]:2)-[#6:4]-[#6:3]-1-[#7:70])-[#6:54]-[#6:55]-[#6:56]-[#7:57])-[#6:33](-[#7:35]-[#6:36](-[#6:39](-[#7:41]-[#6:42](-[#6:50](-[#8:52])=[#8:51])-[#6:43]-[#6:44]1:[#6:49]:[#6:48]:[#6:47]:[#6:46]:[#6:45]:1)=[#8:40])-[#6:37]-[#8:38])=[#8:34])=[#8:30])-[#6:27]-[#8:28])=[#8:24]>>[#8:1]=[#6:2]1-[#7:22]-[#6:17](-[#6:18]-[#6:19](-[#7:21])=[#8:20])-[#6:15](=[#8:16])-[#7:14]-[#6:13]2-[#6:23](-[#7:25]-[#6:26](-[#6:29](-[#7:31]-[#6:32](-[#6:53](-[#6:58]3:[#6:63]:[#6:62]:[#6:61]4:[#6:64](:[#6:65]:[#7:66]:[#6:60]:4:[#6:59]:3)-[#6:12]-2-[#8:11]-[#6:10]2:[#6:67]3:[#7:68]:[#6:69]:[#6:5](:[#6:6]:3:[#6:7]:[#6:8](-Br):[#6:9]:2)-[#6:4]-[#6:3]-1-[#7:70])-[#6:54]-[#6:55]-[#6:56]-[#7:57])-[#6:33](-[#7:35]-[#6:36](-[#6:39](-[#7:41]-[#6:42](-[#6:50](-[#8:52])=[#8:51])-[#6:43]-[#6:44]1:[#6:49]:[#6:48]:[#6:47]:[#6:46]:[#6:45]:1)=[#8:40])-[#6:37]-[#8:38])=[#8:34])=[#8:30])-[#6:27]-[#8:28])=[#8:24]",
            "reactions": [
                {
                    "substrate": "NCCCC1c2ccc3c(c[nH]c3c2)C2Oc3cccc4c(c[nH]c34)CC(N)C(=O)NC(CC(N)=O)C(=O)NC2C(=O)NC(CO)C(=O)NC1C(=O)NC(CO)C(=O)NC(Cc1ccccc1)C(=O)O",
                    "products": [
                        "NCCCC1c2ccc3c(c[nH]c3c2)C2Oc3cc(Br)cc4c(c[nH]c34)CC(N)C(=O)NC(CC(N)=O)C(=O)NC2C(=O)NC(CO)C(=O)NC1C(=O)NC(CO)C(=O)NC(Cc1ccccc1)C(=O)O"
                    ],
                    "isIntermediate": true,
                    "description": "Bromination of darobactin A at the C-8 position of W1, validated by in vitro assay with purified DarHPse, NaBr, FAD, and flavin reductase."
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "Heterologous expression",
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1016/j.chembiol.2023.06.011"
                ]
            },
            "databaseIds": {
                "ec": "1.14.19"
            }
        }
    ]
}