The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases.
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.
Liu
Wen
W
Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Nonaka
Koichi
K
Nie
Liping
L
Zhang
Jian
J
Christenson
Steven D
SD
Bae
Juyun
J
Van Lanen
Steven G
SG
Zazopoulos
Emmanuel
E
Farnet
Chris M
CM
Yang
Catherine F
CF
Shen
Ben
B
D003001:Cloning, Molecular; D023061:Gene Order; D005798:Genes, Bacterial; D005813:Genes, Synthetic / Q000235:genetics*; D005810:Multigene Family / Q000502:physiology*; D048630:Polyketide Synthases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification; D009353:Zinostatin / Q000096:biosynthesis* / Q000737:chemistry
D048630:Polyketide Synthases; D009353:Zinostatin