Quinolidomicin A1 is a 60-membered macrocyclic compound isolated from Micromonospora sp. JY16.[1] Quinolidomicins are a class of macrolides that contain a benzoquinone chromophore as well as an immense lactone ring, which far surpasses that in monozanomycin.[2] It is currently the largest identified macrolide of terrestrial origin.[3] It was initially discovered when in a screening for anti-tumor antibiotics, where it was found to be cytotoxic against P388 murine leukemia cells (IC50 8 nM),[4] and has later been found to have strong cytotoxic activity against HT-29, MKN28, K562, and KB.[5]
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| Names | |
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| IUPAC name
(21Z,23Z,25Z,33Z,35Z,50Z,52Z)-1,7,9,17,19,27,31,37,39,41,45,47,49,55,59-pentadecahydroxy-5-[(1E,3E)-8-(5-hydroxy-2-methylsulfanyl-3,6-dioxocyclohexa-1,4-dien-1-yl)-8-methoxy-5-methylocta-1,3-dienyl]-14,44,48,50,54,56,58-heptamethyl-4,61-dioxabicyclo[55.3.1]henhexaconta-21,23,25,33,35,50,52-heptaene-3,29-dione
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| Identifiers | |
3D model (JSmol)
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| ChemSpider | |
| MeSH | A1 quinolidomicin A1 |
PubChem CID
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| Properties | |
| C83H133NO22S | |
| Molar mass | 1529.02 g·mol−1 |
| Density | 1.3±0.1 g/cm3 |
| Boiling point | 1,444.6 °C (2,632.3 °F; 1,717.8 K) ±65.0[dubious – discuss] |
| Vapor pressure | 0.0±0.6 mmHg |
Refractive index (nD)
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1.597 |
| Hazards | |
| Flash point | 827.5±34.3 °C |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Biosynthesis
editLike many macrocyclic polyketides, quinolidomicin A1 is biosynthesized by type-I polyketide synthases. Decarboxylative condensations for a single-chain elongation are facilitated by β-ketosynthase (KS), acyl transferase (AT), and acyl carrier protein (ACP). The modification domains that contribute to structural variations are dehydratase (DH), enoylreductase (ER), and β-ketoreductase (KR). A module refers to a set of these domains. The acyclic chain is then cut by thioesterase (TE). As this is such a large macrolide, it contains many modules across 13 open reading frames (ORF) to be biosynthesized, the order shown as a sequence of these domains.[6]
References
edit- ^ Hashimoto, Takuya; Hashimoto, Junko; Kozone, Ikuko; Amagai, Keita; Kawahara, Teppei; Takahashi, Shunji; Ikeda, Haruo; Shin-ya, Kazuo (2018-12-13). "Biosynthesis of Quinolidomicin, the Largest Known Macrolide of Terrestrial Origin: Identification and Heterologous Expression of a Biosynthetic Gene Cluster over 200 kb". Organic Letters. 20 (24): 7996–7999. doi:10.1021/acs.orglett.8b03570. ISSN 1523-7060. PMID 30543302. S2CID 56147859.
- ^ NAKAYAMA, H.; FURIHATA, K.; SETO, H.; OTAKA, N. (1982-04-13). "ChemInform Abstract: STRUCTURE OF MONAZOMYCIN, A NEW IONOPHOROUS ANTIBIOTIC". Chemischer Informationsdienst. 13 (15). doi:10.1002/chin.198215350. ISSN 0009-2975.
- ^ HAYAKAWA, YOICHI; MATSUOKA, MICHIKO; SHIN-YA, KAZUO; SETO, HARUO (1993). "Quinolidomicins A1, A2 and B1, novel 60-membered macrolide antibiotics. 1. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity". The Journal of Antibiotics. 46 (10): 1557–1562. doi:10.7164/antibiotics.46.1557. ISSN 0021-8820. PMID 8244883.
- ^ Hayakawa, Yoichi; Shinya, Kazuo; Furihata, Kazuo; Seto, Haruo (April 1993). "Structure of a novel 60-membered macrolide, quinolidomicin A1". Journal of the American Chemical Society. 115 (7): 3014–3015. doi:10.1021/ja00060a075. ISSN 0002-7863.
- ^ Hashimoto, Takuya; Hashimoto, Junko; Kozone, Ikuko; Amagai, Keita; Kawahara, Teppei; Takahashi, Shunji; Ikeda, Haruo; Shin-ya, Kazuo (2018-12-21). "Biosynthesis of Quinolidomicin, the Largest Known Macrolide of Terrestrial Origin: Identification and Heterologous Expression of a Biosynthetic Gene Cluster over 200 kb". Organic Letters. 20 (24): 7996–7999. doi:10.1021/acs.orglett.8b03570. ISSN 1523-7060. PMID 30543302. S2CID 56147859.
- ^ Hashimoto, Takuya; Hashimoto, Junko; Kozone, Ikuko; Amagai, Keita; Kawahara, Teppei; Takahashi, Shunji; Ikeda, Haruo; Shin-ya, Kazuo (2018-12-13). "Biosynthesis of Quinolidomicin, the Largest Known Macrolide of Terrestrial Origin: Identification and Heterologous Expression of a Biosynthetic Gene Cluster over 200 kb". Organic Letters. 20 (24): 7996–7999. doi:10.1021/acs.orglett.8b03570. ISSN 1523-7060. PMID 30543302. S2CID 56147859.