The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases

被引:114
作者
Liu, W
Nonaka, K
Nie, LP
Zhang, J
Christenson, SD
Bae, J
Van Lanen, SG
Zazopoulos, E
Farnet, CM
Yang, CF
Shen, B [1 ]
机构
[1] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI 53705 USA
[2] Univ Wisconsin, Dept Chem, Madison, WI 53705 USA
[3] Ecopia Biosci Inc, Montreal, PQ H4S 2A1, Canada
[4] Rowan Univ, Dept Chem, Glassboro, NJ 08028 USA
来源
CHEMISTRY & BIOLOGY | 2005年 / 12卷 / 03期
关键词
D O I
10.1016/j.chembiol.2004.12.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The biosynthetic gene cluster for the enediyne antitumor antibiotic neocarzinostatin (NCS) was localized to 130 kb continuous DNA from Streptomyces carzinostaticus ATCC15944 and confirmed by gene inactivation. DNA sequence analysis of 92 kb of the cloned region revealed 68 open reading frames (ORFs), 47 of which were determined to constitute the NCS cluster. Sequence analysis of the genes within the NCS cluster suggested dNDP-D-mannose as a precursor for the deoxy aminosugar, revealed two distinct type I polyketide synthases (PKSs), and supported a convergent model for NCS chromophore biosynthesis from the deoxy aminosugar, naphthoic acid, and enediyne core building blocks. These findings shed light into deoxysugar biosynthesis, further support the iterative type I PKS paradigm for enediyne core biosynthesis, and unveil a mechanism for microbial polycyclic aromatic polyketide biosynthesis by an iterative type I PKS.
引用
收藏
页码:293 / 302
页数:10
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