Leinamycin

Leinamycin
Names
	IUPAC name (2R,4′R,6R,9E,11R,13E,15Z)-4′,11-Dihydroxy-2,4′,9-trimethyl-1′-oxospiro[19-thia-3,20-diazabicyclo[15.2.1]icosa-1(20),9,13,15,17-pentaene-6,5′-dithiolane]-3′,4,12-trione
	Other names Streptomyces antibiotic DC-107
Identifiers
CAS Number	120500-15-4;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:80015;
ChemSpider	8024943;
KEGG	C15677;
PubChem CID	9849230;
	InChI InChI=1S/C22H26N2O6S3/c1-13-8-9-22(21(3,29)20(28)32-33(22)30)11-18(27)23-14(2)19-24-15(12-31-19)6-4-5-7-16(25)17(26)10-13/h4-7,10,12,14,17,26,29H,8-9,11H2,1-3H3,(H,23,27)/b6-4-,7-5+,13-10+/t14-,17-,21+,22-,33?/m1/s1 Key: ZHTRILQJTPJGNK-FYBAATNNSA-N;
	SMILES C[C@H]1NC(=O)C[C@@]2(CC\C(C)=C\[C@@H](O)C(=O)\C=C\C=C/c3csc1n3)S(=O)SC(=O)[C@]2(C)O;
Properties
Chemical formula	C22H26N2O6S3
Molar mass	510.64 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	Infobox references

Leinamycin is an 18-membered macrolactam produced by several species of Streptomyces atroolivaceus. This macrolactam has also been shown to exhibit antitumor properties as well as antimicrobial properties against gram-positive and gram-negative bacteria.[1] The presence of a spiro-fused 1,3-dioxo-1,2-dithiolane moiety was a unique structural property at the time of this compound's discovery and it plays an important role in leinamycin's antitumor and antibacterial properties due to its ability to inhibit DNA synthesis.[2][3]

Biosynthesis

The seminal proposal for the biosynthesis of leinamycin was published in Chemistry & Biochemistry in 2004.[4] This biosynthesis consists of a discrete and modular NRPS, AT-less PKSs, and PKS modules. NRPS-PKS assembly line dictates the loading of D-Ala to initiate biosynthesis, followed by the loading of L-Cys to the peptidyl carrier protein (PCP). The dipeptide is then cyclized and oxidized to form the thiazonyl-S-PCP intermediate. The thiazonyl intermediate is then transferred to the PKS assembly line where the backbone is elongated by six units. The leinamycin hybrid peptide-polyketide carbon backbone intermediate is then cyclized by the thioesterase domain (TE) to yield intermediate 1. Methylmalonyl-CoA then condenses at the beta-keto group of 1, yielding 2. A series of tailoring enzymes converts 2 to 4, presumably through intermediate 3 to complete the biosynthesis of leinamycin.

gollark: I see. This definitely seems broader than common definitions in use then.

gollark: And I don't think it'll be shifted significantly by being able to deal with that kind of rare event much better as much as... blind luck, happening to have had relevant opportunities, social skills and intelligence.

gollark: Evolutionary fitness is also not the same as physical fitness.

gollark: That's plausible I guess, but it's possible that many of those could have been avoided (and your definition would count this as "fitness", even). I'm pretty sure it's still less common than, well, other day to day bad things.

gollark: Are those *common*? I don't think I know anyone who's actually experienced any of those. Except maybe animals, very broadly.

References

Kara, Mitsunobu; Asano, Kozo; Kawamoto, Isao; Takiouchi, Toshimitsu; Katsumata, Shigeo; Takahashi, KEI-Ichi; Nakano, Hirofumi (1989). "Leinamycin, a new antitumor antibiotic from Streptomyces; Producing organism, fermentation and isolation". The Journal of Antibiotics. 42 (12): 1768–1774. doi:10.7164/antibiotics.42.1768. PMID 2621160.
Hara, Mitsunobu; Saitoh, Yutaka; Nakano, Hirofumi (1990). "DNA strand scission by the novel antitumor antibiotic leinamycin". Biochemistry. 29 (24): 5676–5681. doi:10.1021/bi00476a005. PMID 2383554.
Asai, Akira; Hara, Mitsunobu; Kakita, Shingo; Kanda, Yutaka; Yoshida, Mayumi; Saito, Hiromitsu; Saitoh, Yutaka (1996). "Thiol-Mediated DNA Alkylation by the Novel Antitumor Antibiotic Leinamycin". Journal of the American Chemical Society. 118 (28): 6802–6803. doi:10.1021/ja960892w.
Tang, Gong-Li; Cheng, Yi-Qiang; Shen, Ben (2004). "Leinamycin Biosynthesis Revealing Unprecedented Architectural Complexity for a Hybrid Polyketide Synthase and Nonribosomal Peptide Synthetase". Chemistry & Biology. 11: 33–45. doi:10.1016/j.chembiol.2003.12.014.

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[1] Kara, Mitsunobu; Asano, Kozo; Kawamoto, Isao; Takiouchi, Toshimitsu; Katsumata, Shigeo; Takahashi, KEI-Ichi; Nakano, Hirofumi (1989). "Leinamycin, a new antitumor antibiotic from Streptomyces; Producing organism, fermentation and isolation". The Journal of Antibiotics. 42 (12): 1768–1774. doi:10.7164/antibiotics.42.1768. PMID 2621160.

[2] Hara, Mitsunobu; Saitoh, Yutaka; Nakano, Hirofumi (1990). "DNA strand scission by the novel antitumor antibiotic leinamycin". Biochemistry. 29 (24): 5676–5681. doi:10.1021/bi00476a005. PMID 2383554.

[3] Asai, Akira; Hara, Mitsunobu; Kakita, Shingo; Kanda, Yutaka; Yoshida, Mayumi; Saito, Hiromitsu; Saitoh, Yutaka (1996). "Thiol-Mediated DNA Alkylation by the Novel Antitumor Antibiotic Leinamycin". Journal of the American Chemical Society. 118 (28): 6802–6803. doi:10.1021/ja960892w.

[4] Tang, Gong-Li; Cheng, Yi-Qiang; Shen, Ben (2004). "Leinamycin Biosynthesis Revealing Unprecedented Architectural Complexity for a Hybrid Polyketide Synthase and Nonribosomal Peptide Synthetase". Chemistry & Biology. 11: 33–45. doi:10.1016/j.chembiol.2003.12.014.