Neocarzinostatin : Cluster information

Compound

Entry name	Neocarzinostatin
Moiety description	A: enediyne core B: naphthoic acid moiety
PKS Type	A: TypeI iterative B: TypeI iterative
Starter Unit	A: acetyl-CoA B: acetyl-CoA
Chain Length	A: 8 B: 6
Sugar Unit	N-methyl-D-fucosamine
Classification	Enediyne
Activity	Antibiotic Antitumor
Composition	C₃₅H₃₃NO₁₂

Original source

Organism	Streptomyces carzinostaticus
Strain	ATCC 15944
Contig	AY117439

PKS/NRPS Module

A	Ncarz_00330 ncsE	1		acetyl-CoA malonyl-CoA
B	Ncarz_00070 ncsB	1		acetyl-CoA malonyl-CoA

KS	2..412

AT	619..835

ACP	956..1057

KR	1237..1420

DH	1489..1644

PPT	1746..1956

KS	1..367

AT	526..841

TH	849..996

KR	1378..1571

ACP	1664..1733

Reference

A genomics-guided approach for discovering and expressing cryptic metabolic pathways.: Zazopoulos E, Huang K, Staffa A, Liu W, Bachmann BO, Nonaka K, Ahlert J, Thorson JS, Shen B, Farnet CM
[PMID: 12536216]Nat Biotechnol. 21 (2003) 187-90
Neocarzinostatin naphthoate synthase: an unique iterative type I PKS from neocarzinostatin producer Streptomyces carzinostaticus.: Sthapit B, Oh TJ, Lamichhane R, Liou K, Lee HC, Kim CG, Sohng JK
[PMID: 15147895]FEBS Lett. 566 (2004) 201-6
The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases.: Liu W, Nonaka K, Nie L, Zhang J, Christenson SD, Bae J, Van Lanen SG, Zazopoulos E, Farnet CM, Yang CF, Shen B
[PMID: 15797213]Chem Biol. 12 (2005) 293-302
Characterization of NcsB2 as a promiscuous naphthoic acid/coenzyme A ligase integral to the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.: Cooke HA, Zhang J, Griffin MA, Nonaka K, Van Lanen SG, Shen B, Bruner SD
[PMID: 17539640]J Am Chem Soc. 129 (2007) 7728-9
A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis.: Zhang J, Van Lanen SG, Ju J, Liu W, Dorrestein PC, Li W, Kelleher NL, Shen B
[PMID: 18223152]Proc Natl Acad Sci U S A. 105 (2008) 1460-5
Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.: Luo Y, Lin S, Zhang J, Cooke HA, Bruner SD, Shen B
[PMID: 18387946]J Biol Chem. 283 (2008) 14694-702
Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.: Cooke HA, Guenther EL, Luo Y, Shen B, Bruner SD
[PMID: 19702337]Biochemistry. 48 (2009) 9590-8
Characterization of the epoxide hydrolase NcsF2 from the neocarzinostatin biosynthetic gene cluster.: Lin S, Horsman GP, Shen B
[PMID: 20704329]Org Lett. 12 (2010) 3816-9
In vivo characterization of NcsB3 to establish the complete biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore.: Hang VT, Oh TJ, Yamaguchi T, Sohng JK
[PMID: 20735485]FEMS Microbiol Lett. 311 (2010) 119-25
Predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of nine-membered enediyne antitumor antibiotics.: Horsman GP, Lechner A, Ohnishi Y, Moore BS, Shen B
[PMID: 23844627]Biochemistry. 52 (2013) 5217-24
Enediyne polyketide synthases stereoselectively reduce the beta-ketoacyl intermediates to beta-D-hydroxyacyl intermediates in enediyne core biosynthesis.: Ge HM, Huang T, Rudolf JD, Lohman JR, Huang SX, Guo X, Shen B
[PMID: 25019332]Org Lett. 16 (2014) 3958-61
Insights into the programmed ketoreduction of partially reducing polyketide synthases: stereo- and substrate-specificity of the ketoreductase domain.: Soehano I, Yang L, Ding F, Sun H, Low ZJ, Liu X, Liang ZX
[PMID: 25238086]Org Biomol Chem. 12 (2014) 8542-9