{
    "accession": "MITE0000240",
    "status": "active",
    "comment": "Reductive cyclization of five- (ikarugamycin) and six-membered (alteramide) rings in polycyclic tetramate macrolactams.",
    "changelog": [
        {
            "version": "1",
            "date": "2026-01-02",
            "contributors": [
                "0000-0002-8834-593X"
            ],
            "reviewers": [
                "0000-0001-6534-6609"
            ],
            "comment": "New entry. Reviewer added descriptions and isoikarugamycin reaction."
        }
    ],
    "enzyme": {
        "name": "OX4",
        "description": "Alcohol dehydrogenase/reductase",
        "references": [
            "doi:10.1021/jacs.5c04971"
        ],
        "databaseIds": {
            "uniprot": "UPI00019B291A",
            "genpept": "ACP19697.1"
        },
        "cofactors": {
            "organic": [
                "NAD",
                "NADP"
            ]
        }
    },
    "reactions": [
        {
            "tailoring": [
                "Cyclization",
                "Reduction"
            ],
            "description": "Reductive cyclization to form a 6-membered ring.",
            "reactionSMARTS": "[#6:1]-[#6:2]-[#6:3]1-[#6:7]2-[#6:31]-[#6:8]3-[#6:11]=[#6:12]-[#6:13]=[#6:14]-[#6:15](-[#7:17]-[#6:18]-[#6:19]-[#6:20]-[#6:21]4-[#7:29]-[#6:27](=[#8:28])-[#6:24](=[#6:25](-[#6:35]=[#6:36]-[#6:34]=[#6:33]-[#6:10](-[#8:32])-[#6:9]-3-[#6:6]-2-[#6:5]-[#6:4]-1-[#6:30])-[#8:26])-[#6:22]-4=[#8:23])=[#8:16]>>[#6:1]-[#6:2]-[#6:3]1-[#6:7]2-[#6:31]-[#6:8]3-[#6:11]4-[#6:12]-[#6:13]=[#6:14]-[#6:15](-[#7:17]-[#6:18]-[#6:19]-[#6:20]-[#6:21]5-[#7:29]-[#6:27](=[#8:28])-[#6:24](=[#6:25](-[#6:35]=[#6:36]-[#6:34]-4-[#6:33]-[#6:10](-[#8:32])-[#6:9]-3-[#6:6]-2-[#6:5]-[#6:4]-1-[#6:30])-[#8:26])-[#6:22]-5=[#8:23])=[#8:16]",
            "reactions": [
                {
                    "substrate": "CCC1C(C)CC2C1CC1C=CC=CC(=O)NCCCC3NC(=O)C(=C(O)C=CC=CC(O)C12)C3=O",
                    "products": [
                        "CCC1C(C)CC2C1CC1C3CC=CC(=O)NCCCC4NC(=O)C(=C(O)C=CC3CC(O)C12)C4=O"
                    ],
                    "isIntermediate": false,
                    "description": "Reductive cyclization of 3-deOH alteramide C, leading to 3-deOH HSAF (Heat Stable Antifungal factor)."
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "Inference from genomic data and chemical structure",
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1021/jacs.5c04971"
                ]
            }
        },
        {
            "tailoring": [
                "Cyclization",
                "Reduction"
            ],
            "description": "Reductive cyclization to form a 5-membered ring.",
            "reactionSMARTS": "[#6:1]1(-[#6:11]-[#6:35])-[#6:5]2-[#6:6]=[#6:9]-[#6:8]3-[#6:13]=[#6:14]-[#6:15]=[#6:16]-[#6:17](=[#8:19])-[#7:18]-[#6:20]-[#6:21]-[#6:22]-[#6:23]4-[#6:25](=[#6:27](-[#6:30](=[#8:32])-[#6:31]=[#6:33]-[#6:34]=[#6:12]-[#6:7]-3-[#6:4]-2-[#6:3]-[#6:2]-1-[#6:10])-[#6:28](=[#8:29])-[#7:24]-4)-[#8:26]>>[#6:1]1(-[#6:11]-[#6:35])-[#6:5]2-[#6:6]=[#6:9]-[#6:8]3-[#6:13]4-[#6:34](-[#6:12]-[#6:7]-3-[#6:4]-2-[#6:3]-[#6:2]-1-[#6:10])-[#6:33]=[#6:31]-[#6:30](=[#8:32])-[#6:27]1-[#6:28](=[#8:29])-[#7:24]-[#6:23](-[#6:25]=1-[#8:26])-[#6:22]-[#6:21]-[#6:20]-[#7:18]-[#6:17](=[#8:19])-[#6:16]=[#6:15]-[#6:14]-4",
            "reactions": [
                {
                    "substrate": "CCC1C(C)CC2C3C=CC=CC(=O)C4=C(O)C(CCCNC(=O)C=CC=CC3C=CC12)NC4=O",
                    "products": [
                        "CCC1C(C)CC2C1C=CC1C3CC=CC(=O)NCCCC4NC(=O)C(=C4O)C(=O)C=CC3CC12"
                    ],
                    "isIntermediate": false,
                    "description": "Reductive cyclization of preikarugamycin intermediate, leading to ikarugamycin."
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1021/jacs.5c04971"
                ]
            }
        },
        {
            "tailoring": [
                "Cyclization",
                "Reduction"
            ],
            "description": "Reductive cyclization to form a 5-membered ring.",
            "reactionSMARTS": "[#6:1]1(-[#6:11]-[#6:35])-[#6:5]2-[#6:6]=[#6:9]-[#6:8]3-[#6:13]=[#6:14]-[#6:15]=[#6:16]-[#6:17](=[#8:19])-[#7:18]-[#6:20]-[#6:21]-[#6:22]-[#6:23]4-[#6:25](=[#6:27](-[#6:30](=[#8:32])-[#6:31]=[#6:33]-[#6:34]=[#6:12]-[#6:7]-3-[#6:4]-2-[#6:3]-[#6:2]-1-[#6:10])-[#6:28](=[#8:29])-[#7:24]-4)-[#8:26]>>[#6:1]1(-[#6:11]-[#6:35])-[#6:5]2-[#6:6]=[#6:9]-[#6:8]3-[#6:13]4-[#6:34](-[#6:12]-[#6:7]-3-[#6:4]-2-[#6:3]-[#6:2]-1-[#6:10])-[#6:33]=[#6:31]-[#6:30](=[#8:32])-[#6:27]1-[#6:28](=[#8:29])-[#7:24]-[#6:23](-[#6:25]=1-[#8:26])-[#6:22]-[#6:21]-[#6:20]-[#7:18]-[#6:17](=[#8:19])-[#6:16]-[#6:15]=[#6:14]-4",
            "reactions": [
                {
                    "substrate": "CCC1C(C)CC2C3C=CC=CC(=O)C4=C(O)C(CCCNC(=O)C=CC=CC3C=CC12)NC4=O",
                    "products": [
                        "CCC1C(C)CC2C1C=CC1C3C=CCC(=O)NCCCC4NC(=O)C(=C4O)C(=O)C=CC3CC12"
                    ],
                    "isIntermediate": false,
                    "description": "Reductive cyclization of preikarugamycin intermediate, leading to isoikarugamycin."
                }
            ],
            "evidence": {
                "evidenceCode": [
                    "In vitro assay"
                ],
                "references": [
                    "doi:10.1021/jacs.5c04971"
                ]
            }
        }
    ]
}