{
    "accession": "MITE0000038",
    "status": "active",
    "changelog": [
        {
            "version": "1",
            "date": "2024-07-30",
            "contributors": [
                "0009-0008-7609-4484"
            ],
            "reviewers": [
                "0000-0001-6534-6609",
                "0000-0003-0443-9902",
                "0000-0002-9747-3423"
            ],
            "comment": "Initial entry. Reviewer 1 partially fixed reactionSMARTS:reactionSMARTS, validation still not passing. Reviewer 1 partially fixed reactions:substrate, validation still not passing. Reviewer 1 partially fixed reactions:products, validation still not passing. Reviewer 2 reworked reaction SMARTS from scratch, reaction passing. Reviewer 2 added information from MITE0000026. Reviewer 3 changed text of enzyme description and enzyme reaction 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": "2026-02-05",
            "contributors": [
                "AAAAAAAAAAAAAAAAAAAAAAAA"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "Fixed typo in reaction description"
        },
        {
            "version": "6",
            "date": "2026-07-02",
            "contributors": [
                "AAAAAAAAAAAAAAAAAAAAAAAA"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "Fixed retired UniProtKB accession with UniParc accession."
        }
    ],
    "enzyme": {
        "name": "OxyA",
        "description": "Cytochrome P450",
        "references": [
            "doi:10.1021/acschembio.7b00456",
            "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"
        ],
        "databaseIds": {
            "uniprot": "UPI00021436EE",
            "genpept": "AEI58868.1",
            "mibig": "BGC0000455"
        },
        "cofactors": {
            "organic": [
                "Heme"
            ],
            "inorganic": [
                "Fe"
            ]
        }
    },
    "reactions": [
        {
            "tailoring": [
                "Cyclization",
                "Oxidation"
            ],
            "description": "Introduces the second biaryl-ether crosslink between bht2 and hpg4 in the vancomycin and balhimycin precursor. The reaction occurs while the vancomycin precursor is bound to the PCP of module 6 or 7. The enzyme only accepts the chlorinated precursor.",
            "reactionSMARTS": "[#6:78]-[#7:77]-[#6@H:76](-[#6:75]-[#6:74](-[#6:72])-[#6:73])-[#6:71](=[O:70])-[#7:69]-[#6@H:68](-[#6@@H:3](-[#8:2])-[c:7]1[c:8][c:9][c:10](-[#8:101])[c:5]([Cl:4])[c:6]1)-[#6:67](=[O:66])-[#7:65]-[#6@@H:64](-[#6:63]-[#6:62](-[#7:61])=[O:60])-[#6:59](=[O:58])-[#7:57]-[#6@@H:56]-1-[c:15]2[c:16][c:17][c:12](-[#8:11])[c:13](-[#8:18]-[c:21]3[c:20][c:19][c:24]([c:23][c:22]3[Cl:1])-[#6@H:26](-[#8:25])-[#6@H:48](-[#7:49]-[#6:51](=[O:50])-[#6@H:52](-[#7:53]-[#6:55]-1=[O:54])-[c:31]1[c:30][c:29][c:28](-[#8:27])[c:33][c:32]1)-[#6:47](=[O:46])-[#7:45]-[#6@H:44](-[#6:43](=[O:42])-[#16:99]-[#6:98]-[#6:97]-[#7:96]-[#6:94](=[O:95])-[#6:93]-[#6:92]-[#7:91]-[#6:89](=[O:90])-[#6@H:88](-[#8:100])[C:80]([#6:79])([#6:81])[#6:82]-[#8:83][P:84]([#8:86])([#8:87])=[O:85])-[c:41]1[c:34][c:36](-[#8:35])[c:37][c:39](-[#8:38])[c:40]1)[c:14]2>>[#6:78]-[#7:77]-[#6@H:76](-[#6:75]-[#6:74](-[#6:73])-[#6:72])-[#6:71](=[O:70])-[#7:69]-[#6@@H:68]-1-[#6@@H:3](-[#8:2])-[c:7]2[c:8][c:9][c:10](-[#8:101]-[c:17]3[c:16][c:15]-4[c:14][c:13](-[#8:18]-[c:21]5[c:20][c:19][c:24]([c:23][c:22]5[Cl:1])-[#6@H:26](-[#8:25])-[#6@H:48](-[#7:49]-[#6:51](=[O:50])-[#6@H:52](-[#7:53]-[#6:55](=[O:54])-[#6@@H:56]-4-[#7:57]-[#6:59](=[O:58])-[#6@H:64](-[#6:63]-[#6:62](-[#7:61])=[O:60])-[#7:65]-[#6:67]-1=[O:66])-[c:31]1[c:32][c:33][c:28](-[#8:27])[c:29][c:30]1)-[#6:47](=[O:46])-[#7:45]-[#6@H:44](-[#6:43](=[O:42])-[#16:99]-[#6:98]-[#6:97]-[#7:96]-[#6:94](=[O:95])-[#6:93]-[#6:92]-[#7:91]-[#6:89](=[O:90])-[#6@H:88](-[#8:100])[C:80]([#6:81])([#6:79])[#6:82]-[#8:83][P:84]([#8:87])([#8:86])=[O:85])-[c:41]1[c:40][c:39](-[#8:38])[c:37][c:36](-[#8:35])[c:34]1)[c:12]3-[#8:11])[c:5]([Cl:4])[c:6]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]1C(=O)N[C@H](c2ccc(O)cc2)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)c2cc(O)cc(O)c2)[C@@H](O)c2ccc(c(Cl)c2)Oc2cc1ccc2O)[C@@H](O)c1ccc(O)c(Cl)c1",
                    "products": [
                        "CN[C@H](CC(C)C)C(=O)N[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H]2C(=O)N[C@H](c3ccc(O)cc3)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)c3cc(O)cc(O)c3)[C@@H](O)c3ccc(c(Cl)c3)Oc3cc2cc(c3O)Oc2ccc(cc2Cl)[C@@H]1O"
                    ],
                    "isIntermediate": true,
                    "description": "Introduces the second biaryl-ether crosslink between bht2 and hpg4 in the vancomycin and balhimycin precursor"
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1021/acschembio.7b00456"
                ]
            }
        },
        {
            "tailoring": [
                "Cyclization",
                "Oxidation"
            ],
            "description": "The reaction might be less specific than depicted in the reaction SMARTS. There is no detailed study on the specificity so far. The reaction occurs probably while the precursor peptide backbone is bound to the NRPS as shown for the closely related vancomycin biosynthesis (doi:10.1002/ANIE.200461278).",
            "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]1-[#6:42](=[#8:43])-[#7:41]-[#6:33](-[#6:34]2:[#6:40]:[#6:39]:[#6:37](-[#8:38]):[#6:36]:[#6:35]:2)-[#6:31](=[#8:32])-[#7:30]-[#6:26](-[#6:27](-[#8:29])=[#8:28])-[#6:24](-[#8:25])-[#6:21]2:[#6:22]:[#6:23]:[#6:18](:[#6:19](-[Cl:44]):[#6:20]:2)-[#8:17]-[#6:16]2:[#6:45](:[#6:47]:[#6:48]:[#6:14]-1:[#6:15]:2)-[#8:46]>>[#6:1]-[#6:2](-[#6:67])-[#6:3]-[#6:4](-[#7:66])-[#6:5](=[#8:65])-[#7:6]-[#6:7]1-[#6:55](-[#8:64])-[#6:56]2:[#6:63]:[#6:62]:[#6:60](-[#8:61]-[#6:47]3:[#6:48]:[#6:14]4:[#6:15]:[#6:16](:[#6:45]:3-[#8:46])-[#8:17]-[#6:18]3:[#6:23]:[#6:22]:[#6:21](-[#6:24](-[#6:26](-[#7:30]-[#6:31](-[#6:33](-[#7:41]-[#6:42](=[#8:43])-[#6:13]-4-[#7:12]-[#6:11](=[#8:49])-[#6:10](-[#6:50]-[#6:51](-[#7:53])=[#8:52])-[#7:9]-[#6:8]-1=[#8:54])-[#6:34]1:[#6:40]:[#6:39]:[#6:37](-[#8:38]):[#6:36]:[#6:35]:1)=[#8:32])-[#6:27](-[#8:29])=[#8:28])-[#8:25]):[#6:20]:[#6:19]:3-[Cl:44]):[#6:58](-[Cl:59]):[#6:57]:2",
            "reactions": [
                {
                    "substrate": "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",
                    "products": [
                        "CC(C)CC(N)C(=O)NC1C(=O)NC(CC(N)=O)C(=O)NC2C(=O)NC(c3ccc(O)cc3)C(=O)NC(C(=O)O)C(O)c3ccc(c(Cl)c3)Oc3cc2cc(c3O)Oc2ccc(cc2Cl)C1O"
                    ],
                    "isIntermediate": true
                }
            ],
            "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"
                ]
            }
        }
    ]
}