{
    "accession": "MITE0000041",
    "status": "active",
    "changelog": [
        {
            "version": "1",
            "date": "2024-07-30",
            "contributors": [
                "0009-0008-7609-4484"
            ],
            "reviewers": [
                "0000-0001-6534-6609",
                "0000-0002-9747-3423"
            ],
            "comment": "Initial entry. Reviewer 1 fixed reaction SMARTS formatting. Reviewer 1 added information from MITE0000025. Reviewer 2 changed enzyme description."
        },
        {
            "version": "2",
            "date": "2025-07-25",
            "contributors": [
                "AAAAAAAAAAAAAAAAAAAAAAAA"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "Added cofactor information"
        },
        {
            "version": "3",
            "date": "2025-08-13",
            "contributors": [
                "AAAAAAAAAAAAAAAAAAAAAAAA"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "Fixed URL formatting"
        },
        {
            "version": "4",
            "date": "2025-08-26",
            "contributors": [
                "AAAAAAAAAAAAAAAAAAAAAAAA"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "Homogenized enzyme descriptions"
        },
        {
            "version": "5",
            "date": "2026-07-02",
            "contributors": [
                "AAAAAAAAAAAAAAAAAAAAAAAA"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "Fixed retired UniProtKB accession with UniParc accession."
        }
    ],
    "enzyme": {
        "name": "OxyB",
        "description": "Cytochrome P450",
        "references": [
            "doi:10.1016/j.jbiotec.2006.04.009",
            "doi:10.1128/AAC.43.7.1565",
            "doi:10.1002/1521-3773(20011217)40:24<4688::AID-ANIE4688>3.0.CO;2-M",
            "doi:10.1021/ja071038f",
            "doi:10.1002/ANIE.200461278"
        ],
        "databaseIds": {
            "uniprot": "UPI00021436EF",
            "genpept": "AEI58869.1",
            "mibig": "BGC0000455"
        },
        "cofactors": {
            "inorganic": [
                "Fe"
            ],
            "organic": [
                "Heme"
            ]
        }
    },
    "reactions": [
        {
            "tailoring": [
                "Cyclization",
                "Oxidation"
            ],
            "description": "Introduces the first biaryl-ether crosslink between hpg4 and bht6 in the vancomycin and balhimycin precursors. Reaction occurs while the backbone precursor is bound to the PCP domain of module 6 or 7. The link to the PCP domain is required for the reaction.",
            "reactionSMARTS": "[#6:23]-[#7:24]-[#6@H:25](-[#6:26]-[#6:27](-[#6:28])-[#6:29])-[#6:30](=[O:31])-[#7:32]-[#6@H:33](-[#6@@H:84](-[#8:85])-[c:81]1[c:80][c:79][c:78](-[#8:87])[c:83][c:82]1)-[#6:34](=[O:35])-[#7:36]-[#6@@H:37](-[#6:38]-[#6:39](-[#7:40])=[O:41])-[#6:42](=[O:43])-[#7:44]-[#6@@H:45](-[#6:46](=[O:47])-[#7:48]-[#6@@H:49](-[#6:50](=[O:51])-[#7:52]-[#6@@H:53](-[#6@@H:63](-[#8:64])-[c:65]1[c:66][c:67][c:68](-[#8:86])[c:69][c:70]1)-[#6:54](=[O:55])-[#16:21]-[#6:20]-[#6:19]-[#7:18]-[#6:16](=[O:17])-[#6:15]-[#6:14]-[#7:13]-[#6:11](=[O:12])-[#6@H:10](-[#8:22])[C:2]([#6:1])([#6:3])[#6:4]-[#8:5][P:6]([#8:8])([#8:9])=[O:7])-[c:58]1[c:57][c:56][c:61](-[#8:62])[c:60][c:59]1)-[c:73]1[c:72][c:71][c:76](-[#8:77])[c:75][c:74]1>>[#6:23]-[#7:24]-[#6@H:25](-[#6:26]-[#6:27](-[#6:29])-[#6:28])-[#6:30](=[O:31])-[#7:32]-[#6@H:33](-[#6@@H:84](-[#8:85])-[c:81]1[c:82][c:83][c:78](-[#8:87])[c:79][c:80]1)-[#6:34](=[O:35])-[#7:36]-[#6@@H:37](-[#6:38]-[#6:39](-[#7:40])=[O:41])-[#6:42](=[O:43])-[#7:44]-[#6@@H:45]-1-[c:73]2[c:72][c:71][c:76](-[#8:77])[c:75](-[#8:86]-[c:68]3[c:69][c:70][c:65]([c:66][c:67]3)-[#6@H:63](-[#8:64])-[#6@H:53](-[#7:52]-[#6:50](=[O:51])-[#6@H:49](-[#7:48]-[#6:46]-1=[O:47])-[c:58]1[c:59][c:60][c:61](-[#8:62])[c:56][c:57]1)-[#6:54](=[O:55])-[#16:21]-[#6:20]-[#6:19]-[#7:18]-[#6:16](=[O:17])-[#6:15]-[#6:14]-[#7:13]-[#6:11](=[O:12])-[#6@H:10](-[#8:22])[C:2]([#6:3])([#6:1])[#6:4]-[#8:5][P:6]([#8:9])([#8:8])=[O:7])[c:74]2",
            "reactions": [
                {
                    "substrate": "CN[C@H](CC(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(=O)(O)O)[C@@H](O)c1ccc(O)cc1)c1ccc(O)cc1)c1ccc(O)cc1)[C@@H](O)c1ccc(O)cc1",
                    "products": [
                        "CN[C@H](CC(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H]1C(=O)N[C@H](c2ccc(O)cc2)C(=O)N[C@H](C(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(=O)(O)O)[C@@H](O)c2ccc(cc2)Oc2cc1ccc2O)[C@@H](O)c1ccc(O)cc1"
                    ],
                    "isIntermediate": true
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1002/ANIE.200461278",
                    "doi:10.1021/ja071038f"
                ]
            }
        },
        {
            "tailoring": [
                "Cyclization"
            ],
            "description": "The reaction probably occurs on the PCP bound precursor.",
            "reactionSMARTS": "[#6:1]-[#6:2](-[#6:67])-[#6:3]-[#6:4](-[#7:66])-[#6:5](=[#8:65])-[#7:6]-[#6:7](-[#6:55](-[#8:64])-[#6:56]1:[#6:63]:[#6:62]:[#6:60](-[#8:61]):[#6:58](-[Cl:59]):[#6:57]:1)-[#6:8](=[#8:54])-[#7:9]-[#6:10](-[#6:50]-[#6:51](-[#7:53])=[#8:52])-[#6:11](=[#8:49])-[#7:12]-[#6:13](-[#6:21](=[#8:48])-[#7:22]-[#6:23](-[#6:31](=[#8:47])-[#7:32]-[#6:33](-[#6:37](-[#8:46])-[#6:38]1:[#6:45]:[#6:44]:[#6:42](-[#8:43]):[#6:40](-[Cl:41]):[#6:39]:1)-[#6:34](-[#8:36])=[#8:35])-[#6:24]1:[#6:30]:[#6:29]:[#6:27](-[#8:28]):[#6:26]:[#6:25]:1)-[#6:14]1:[#6:20]:[#6:19]:[#6:17](-[#8:18]):[#6:16]:[#6:15]:1>>[#6:1]-[#6:2](-[#6:67])-[#6:3]-[#6:4](-[#7:66])-[#6:5](=[#8:65])-[#7:6]-[#6:7](-[#6:55](-[#8:64])-[#6:56]1:[#6:63]:[#6:62]:[#6:60](-[#8:61]):[#6:58](-[Cl:59]):[#6:57]:1)-[#6:8](=[#8:54])-[#7:9]-[#6:10](-[#6:50]-[#6:51](-[#7:53])=[#8:52])-[#6:11](=[#8:49])-[#7:12]-[#6:13]1-[#6:21](=[#8:48])-[#7:22]-[#6:23](-[#6:24]2:[#6:25]:[#6:26]:[#6:27](-[#8:28]):[#6:29]:[#6:30]:2)-[#6:31](=[#8:47])-[#7:32]-[#6:33](-[#6:34](-[#8:36])=[#8:35])-[#6:37](-[#8:46])-[#6:38]2:[#6:45]:[#6:44]:[#6:42](:[#6:40](-[Cl:41]):[#6:39]:2)-[#8:43]-[#6:16]2:[#6:17](:[#6:19]:[#6:20]:[#6:14]-1:[#6:15]:2)-[#8:18]",
            "reactions": [
                {
                    "substrate": "CC(C)CC(N)C(=O)NC(C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(C(=O)NC(C(=O)O)C(O)c1ccc(O)c(Cl)c1)c1ccc(O)cc1)c1ccc(O)cc1)C(O)c1ccc(O)c(Cl)c1",
                    "products": [
                        "CC(C)CC(N)C(=O)NC(C(=O)NC(CC(N)=O)C(=O)NC1C(=O)NC(c2ccc(O)cc2)C(=O)NC(C(=O)O)C(O)c2ccc(c(Cl)c2)Oc2cc1ccc2O)C(O)c1ccc(O)c(Cl)c1"
                    ],
                    "isIntermediate": true,
                    "description": "The reaction might be less specific than depicted in the reaction SMARTS. There is no detailed study on the specificity so far. Furthermore, the substrate probably needs to be bound to a PCP domain in order to be recognized."
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "Knock-out studies"
                ],
                "references": [
                    "doi:10.1002/1521-3773(20011217)40:24<4688::AID-ANIE4688>3.0.CO;2-M",
                    "doi:10.1016/j.jbiotec.2006.04.009"
                ]
            }
        }
    ]
}