{
    "accession": "MITE0000239",
    "status": "active",
    "comment": "Reductive cyclization of five-membered ring (ikarugamycin) in polycyclic tetramate macrolactams.",
    "changelog": [
        {
            "version": "1",
            "date": "2026-01-08",
            "contributors": [
                "0000-0002-8834-593X"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "New entry. Reviewer modified descriptions."
        }
    ],
    "enzyme": {
        "name": "IkaC",
        "description": "Alcohol dehydrogenase/reductase",
        "references": [
            "doi:10.1021/jacs.5c04971"
        ],
        "databaseIds": {
            "uniprot": "UPI000588A50D",
            "genpept": "AJD77025.1",
            "mibig": "BGC0001435"
        },
        "cofactors": {
            "organic": [
                "NAD",
                "NADP"
            ]
        }
    },
    "reactions": [
        {
            "tailoring": [
                "Cyclization",
                "Reduction"
            ],
            "description": "Reductive cyclization to form a 5-membered ring in ikarugamycin pathway.",
            "reactionSMARTS": "[#6:1]-[#6:2]-[#6:3]1-[#6:31](-[#6:32])-[#6:30]-[#6:29]2-[#6:4]-1-[#6:5]=[#6:6]-[#6:7]1-[#6:28]-2-[#6:27]=[#6:26]-[#6:25]=[#6:24]-[#6:22](-[#8:23])=[#6:21]2-[#6:33](=[#8:34])-[#6:17](-[#7:18]-[#6:19]-2=[#8:20])-[#6:16]-[#6:15]-[#6:14]-[#7:13]-[#6:12](=[#8:35])-[#6:11]=[#6:10]-[#6:9]=[#6:8]-1>>[#6:1]-[#6:2]-[#6:3]1-[#6:31](-[#6:32])-[#6:30]-[#6:29]2-[#6:4]-1-[#6:5]=[#6:6]-[#6:7]1-[#6:28]-2-[#6:27]-[#6:26]2-[#6:8]-1-[#6:9]-[#6:10]=[#6:11]-[#6:12](=[#8:35])-[#7:13]-[#6:14]-[#6:15]-[#6:16]-[#6:17]1-[#6:33](=[#8:34])-[#6:21](=[#6:22](-[#6:24]=[#6:25]-2)-[#8:23])-[#6:19](=[#8:20])-[#7:18]-1",
            "reactions": [
                {
                    "substrate": "CCC1C(C)CC2C3C=CC=CC(O)=C4C(=O)NC(CCCNC(=O)C=CC=CC3C=CC12)C4=O",
                    "products": [
                        "CCC1C(C)CC2C1C=CC1C3CC=CC(=O)NCCCC4NC(=O)C(=C(O)C=CC3CC12)C4=O"
                    ],
                    "isIntermediate": false,
                    "description": "Reductive cyclization of preikarugamycin intermediate, leading to ikarugamycin."
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1021/jacs.5c04971"
                ]
            }
        }
    ]
}