{
    "accession": "MITE0000034",
    "status": "active",
    "comment": "The enzyme seems to be highly specific for the backbone of teicoplanin, as it does not recognize the closely related vancomycin aglycone.",
    "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 but had to remove the balanced substrate/product SMILES due to issues with phosphorous chemistry in RDKit. Reviewer 2 modified enzyme name and reaction description"
        }
    ],
    "enzyme": {
        "name": "GtfA",
        "description": "Glycosyltransferase",
        "references": [
            "doi:10.1099/mic.0.26507-0",
            "doi:10.1021/ja0735857",
            "doi:10.1016/S1074-5521(04)00002-X"
        ],
        "databaseIds": {
            "uniprot": "Q6ZZJ7",
            "genpept": "CAE53349.1",
            "mibig": "BGC0000440"
        }
    },
    "reactions": [
        {
            "tailoring": [
                "Glycosylation"
            ],
            "description": " Glycosyltransferase adds N-acetylglucosamine to Bht6 of the teicoplanin precursor. Substrate specificity is probably more general than depicted in the reaction SMARTS, but there is no precise information on substrate specificity. In order to avoid making the reaction too general, the complete backbone is included in the pattern.",
            "reactionSMARTS": "[#6:1]-[#6:2](=[#8:99])-[#7:3]/[#6@@:4]1-[#6@@:97](\\[#8:98])-[#6@:95](/[#8:96])-[#6@@:92](\\[#6:93]-[#8:94])-[#8:91]-[#6@:5]-1\\[#8:6]-[#6:7]1:[#6:57]2:[#6:58]:[#6:59]3:[#6:60]:[#6:8]:1-[#8:9]-[#6:10]1:[#6:90]:[#6:89]:[#6:14](-[#6@@:15](/[#8:88])-[#6@@:16]4-[#7:87]-[#6:85](=[#8:86])-[#6@:39](-[#7:40]-[#6:41](=[#8:84])\\[#6@@:42]-3-[#7:43]-[#6:44](=[#8:83])\\[#6@@:45]3-[#6:78]5:[#6:79]:[#6:80](-[#8:82]):[#6:81]:[#6:76](:[#6:77]:5)-[#8:75]-[#6:70]5:[#6:71](-[#8:74]):[#6:72]:[#6:73]:[#6:68](:[#6:69]:5)-[#6@@:66](/[#7:67])-[#6:64](=[#8:65])-[#7:63]-[#6@:49](-[#6:50]-[#6:51]5:[#6:62]:[#6:61]:[#6:55](-[#8:56]-2):[#6:53](-[Cl:54]):[#6:52]:5)\\[#6:47](=[#8:48])-[#7:46]-3)/[#6:34]2:[#6:35]:[#6:36]:[#6:37](-[#8:38]):[#6:32](:[#6:33]:2)-[#6:25]2:[#6:26](-[#8:31]):[#6:27]:[#6:28](-[#8:30]):[#6:29]:[#6:24]:2-[#6@@:20](/[#6:21](-[#8:23])=[#8:22])-[#7:19]-[#6:17]/4=[#8:18]):[#6:13]:[#6:11]:1-[Cl:12]>>[#6]-[#6](-[#7]\\[#6@]1-[#6@](/[#8:88]\\[#6@:15]2-[#6@:16]3-[#6:17](-[#7:19]-[#6@@:20](-[#6:24]4:[#6:29]:[#6:28](-[#8:30]):[#6:27]:[#6:26](-[#8:31]):[#6:25]:4-[#6:32]4:[#6:33]:[#6:34](-[#6@:39](-[#6:85](-[#7:87]\\3)=[#8:86])\\[#7:40]-[#6:41](=[#8:84])-[#6@@:42]3-[#7:43]-[#6:44](/[#6@:45]5-[#7:46]-[#6:47](=[#8:48])-[#6@@:49](-[#6:50]-[#6:51]6:[#6:52]:[#6:53](-[Cl:54]):[#6:55](-[#8:56]-[#6:57]7:[#6:58]:[#6:59]/3:[#6:60]:[#6:8](:[#6:7]:7-[#8:6]/[#6@@:5]3-[#8:91]-[#6@:92](/[#6:93]-[#8:94])-[#6@@:95](\\[#8:96])-[#6@:97](/[#8:98])-[#6@:4]-3\\[#7:3]-[#6:2](=[#8:99])-[#6:1])-[#8:9]-[#6:10]3:[#6:11](:[#6:13]:[#6:14]-2:[#6:89]:[#6:90]:3)-[Cl:12]):[#6:61]:[#6:62]:6)/[#7:63]-[#6:64](=[#8:65])-[#6@:66](\\[#7:67])-[#6:68]2:[#6:69]:[#6:70](:[#6:71](:[#6:72]:[#6:73]:2)-[#8:74])-[#8:75]-[#6:76]2:[#6:77]:[#6:78]-5:[#6:79]:[#6:80](:[#6:81]:2)-[#8:82])=[#8:83]):[#6:35]:[#6:36]:[#6:37]:4-[#8:38])\\[#6:21](=[#8:22])-[#8:23])=[#8:18])-[#8]-[#6@](/[#6]-[#8])-[#6@@](\\[#8])-[#6@@]-1/[#8])=[#8]",
            "reactions": [
                {
                    "substrate": "CC(=O)N[C@H]1[C@H](Oc2c3cc4cc2Oc2ccc(cc2Cl)[C@@H](O)[C@@H]2NC(=O)[C@H](NC(=O)[C@@H]4NC(=O)[C@H]4NC(=O)[C@@H](Cc5ccc(c(Cl)c5)O3)NC(=O)[C@H](N)c3ccc(O)c(c3)Oc3cc(O)cc4c3)c3ccc(O)c(c3)-c3c(O)cc(O)cc3[C@@H](C(=O)O)NC2=O)O[C@H](CO)[C@@H](O)[C@@H]1O",
                    "products": [
                        "CC(=O)N[C@H]1[C@H](Oc2c3cc4cc2Oc2ccc(cc2Cl)[C@@H](O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2NC(C)=O)[C@@H]2NC(=O)[C@H](NC(=O)[C@@H]4NC(=O)[C@H]4NC(=O)[C@@H](Cc5ccc(c(Cl)c5)O3)NC(=O)[C@H](N)c3ccc(O)c(c3)Oc3cc(O)cc4c3)c3ccc(O)c(c3)-c3c(O)cc(O)cc3[C@@H](C(=O)O)NC2=O)O[C@H](CO)[C@@H](O)[C@@H]1O"
                    ],
                    "isIntermediate": true
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1016/S1074-5521(04)00002-X",
                    "doi:10.1099/mic.0.26507-0",
                    "doi:10.1021/ja0735857"
                ]
            }
        },
        {
            "tailoring": [
                "Glycosylation"
            ],
            "description": " Glycosyltransferase adds N-acetylglucosamine to Bht6 of the teicoplanin precursor. Substrate specificity is probably more general than depicted in the reaction SMARTS, but there is no precise information on substrate specificity. In order to avoid making the reaction too general, the complete backbone is included in the pattern.",
            "reactionSMARTS": "[#8:1]-[#6:2]1:[#6:52]2:[#6:53]:[#6:54]3:[#6:55]:[#6:3]:1-[#8:4]-[#6:5]1:[#6:85]:[#6:84]:[#6:9](-[#6@@:10](/[#8:83])-[#6@@:11]4-[#7:82]-[#6:80](=[#8:81])-[#6@:34](-[#7:35]-[#6:36](=[#8:79])\\[#6@@:37]-3-[#7:38]-[#6:39](=[#8:78])\\[#6@@:40]3-[#6:73]5:[#6:74]:[#6:75](-[#8:77]):[#6:76]:[#6:71](:[#6:72]:5)-[#8:70]-[#6:65]5:[#6:66](-[#8:69]):[#6:67]:[#6:68]:[#6:63](:[#6:64]:5)-[#6@@:61](/[#7:62])-[#6:59](=[#8:60])-[#7:58]-[#6@:44](-[#6:45]-[#6:46]5:[#6:57]:[#6:56]:[#6:50](-[#8:51]-2):[#6:48](-[Cl:49]):[#6:47]:5)\\[#6:42](=[#8:43])-[#7:41]-3)/[#6:29]2:[#6:30]:[#6:31]:[#6:32](-[#8:33]):[#6:27](:[#6:28]:2)-[#6:20]2:[#6:21](-[#8:26]):[#6:22]:[#6:23](-[#8:25]):[#6:24]:[#6:19]:2-[#6@@:15](/[#6:16](-[#8:18])=[#8:17])-[#7:14]-[#6:12]/4=[#8:13]):[#6:8]:[#6:6]:1-[Cl:7]>>[#6]-[#6](-[#7]\\[#6@]1-[#6@](/[#8:83]\\[#6@:10]2-[#6@:11]3-[#6:12](-[#7:14]-[#6@@:15](-[#6:19]4:[#6:24]:[#6:23](-[#8:25]):[#6:22]:[#6:21](-[#8:26]):[#6:20]:4-[#6:27]4:[#6:28]:[#6:29](-[#6@:34](-[#6:80](-[#7:82]\\3)=[#8:81])\\[#7:35]-[#6:36](=[#8:79])-[#6@@:37]3-[#7:38]-[#6:39](/[#6@:40]5-[#7:41]-[#6:42](=[#8:43])-[#6@@:44](-[#6:45]-[#6:46]6:[#6:47]:[#6:48](-[Cl:49]):[#6:50](-[#8:51]-[#6:52]7:[#6:53]:[#6:54]/3:[#6:55]:[#6:3](:[#6:2]:7-[#8:1])-[#8:4]-[#6:5]3:[#6:6](:[#6:8]:[#6:9]-2:[#6:84]:[#6:85]:3)-[Cl:7]):[#6:56]:[#6:57]:6)/[#7:58]-[#6:59](=[#8:60])-[#6@:61](\\[#7:62])-[#6:63]2:[#6:64]:[#6:65](:[#6:66](:[#6:67]:[#6:68]:2)-[#8:69])-[#8:70]-[#6:71]2:[#6:72]:[#6:73]-5:[#6:74]:[#6:75](:[#6:76]:2)-[#8:77])=[#8:78]):[#6:30]:[#6:31]:[#6:32]:4-[#8:33])\\[#6:16](=[#8:17])-[#8:18])=[#8:13])-[#8]-[#6@](/[#6]-[#8])-[#6@@](\\[#8])-[#6@@]-1/[#8])=[#8]",
            "reactions": [
                {
                    "substrate": "N[C@H]1C(=O)N[C@@H]2Cc3ccc(c(Cl)c3)Oc3cc4cc(c3O)Oc3ccc(cc3Cl)[C@@H](O)[C@@H]3NC(=O)[C@H](NC(=O)[C@@H]4NC(=O)[C@@H](NC2=O)c2cc(O)cc(c2)Oc2cc1ccc2O)c1ccc(O)c(c1)-c1c(O)cc(O)cc1[C@@H](C(=O)O)NC3=O",
                    "products": [
                        "CC(=O)N[C@H]1[C@H](O[C@@H]2c3ccc(c(Cl)c3)Oc3cc4cc(c3O)Oc3ccc(cc3Cl)C[C@H]3NC(=O)[C@H](N)c5ccc(O)c(c5)Oc5cc(O)cc(c5)[C@H](NC3=O)C(=O)N[C@H]4C(=O)N[C@H]3C(=O)N[C@@H]2C(=O)N[C@H](C(=O)O)c2cc(O)cc(O)c2-c2cc3ccc2O)O[C@H](CO)[C@@H](O)[C@@H]1O"
                    ],
                    "isIntermediate": true,
                    "description": "kinetically less favored reaction, reaction on monoglycosylated product is favored."
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1016/S1074-5521(04)00002-X",
                    "doi:10.1099/mic.0.26507-0",
                    "doi:10.1021/ja0735857"
                ]
            }
        }
    ]
}