Quinolidomicin

Quinolidomicin A1
Names
	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
Identifiers
CAS Number	148504-47-6;
3D model (JSmol)	Interactive image; Interactive image;
ChemSpider	10291294;
MeSH	A1 quinolidomicin A1
PubChem CID	101656815;
	InChI InChI=1S/C83H132O23S/c1-51-24-19-21-32-63(88)44-68(93)46-69(33-22-20-25-52(2)35-39-75(104-9)77-80(102)72(96)48-73(97)82(77)107-10)105-76(99)50-83(103)49-74(98)57(7)81(106-83)58(8)79(101)55(5)27-23-26-54(4)78(100)56(6)71(95)47-70(94)53(3)36-38-65(90)45-67(92)43-62(87)31-18-14-17-30-61(86)42-66(91)41-60(85)29-16-13-11-12-15-28-59(84)40-64(89)37-34-51/h11-18,20,22-23,25-27,29,31,33,48,51-53,55-65,67-71,74-75,78-79,81,84-90,92-96,98,100-101,103H,19,21,24,28,30,32,34-47,49-50H2,1-10H3/b13-11-,15-12-,17-14-,25-20+,27-23-,29-16-,31-18-,33-22+,54-26- Key: ICRSVVBHIOAZHM-VRIDVCIJSA-N;
	SMILES CC1CCCCC(CC(CC(OC(=O)CC2(CC(C(C(O2)C(C(C(C=CC=C(C(C(C(CC(C(CCC(CC(CC(C=CC=CCC(CC(=O)CC(C=CC=CC=CCC(CC(CC1)O)O)O)O)O)O)O)C)O)O)C)O)C)C)O)C)C)O)O)C=CC=CC(C)CCC(C3=C(C(=O)C=C(C3=O)O)SC)OC)O)O; CC1CCCCC(CC(CC(OC(=O)CC2(CC(C(C(O2)C(C(C(/C=C\C=C(/C(C(C(CC(C(CCC(CC(CC(/C=C\C=C/CC(CC(=O)CC(/C=C\C=C/C=C\CC(CC(CC1)O)O)O)O)O)O)O)C)O)O)C)O)\C)C)O)C)C)O)O)/C=C/C=C/C(C)CCC(C3=C(C(=O)C=C(C3=O)O)SC)OC)O)O;
Properties
Chemical formula	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)	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). Infobox references

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]

Biosynthesis[edit]

Like 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.

[1] 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.

[2] 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.

[3] 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.

[4] 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.

[5] 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.

[6] 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.

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