TY - JOUR
T1 - Characterization of NcsB2 as a promiscuous naphthoic acid/coenzyme A ligase integral to the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin
AU - Cooke, Heather A.
AU - Zhang, Jian
AU - Griffin, Meghan A.
AU - Nonaka, Koichi
AU - Van Lanen, Steven G.
AU - Shen, Ben
AU - Bruner, Steven D.
PY - 2007/6/27
Y1 - 2007/6/27
N2 - The enediyne antitumor antibiotic neocarzinostatin (NCS) is produced by Streptomyces carzinostaticus ATCC15944. The biosynthetic pathway for the naphthoic acid moiety (boxed) of the NCS chromophore (1) is proposed to comprise five enzymes: NcsB, NcsB1, NcsB2, NcsB3, NcsB4. Both in vivo and in vitro experiments were used to support the proposed pathway. NcsB2 was characterized for the ability to catalyze the activation of 2-hydroxy-7-methoxy-5-methyl-1-naphthoic acid (3) via a naphthoyl-AMP ester (5) and subsequent formation of the corresponding coenzyme A ester. The finding that NcsB2 exhibits promiscuous substrate specificity toward a diverse set of naphthoic acid analogues with 2-, 5-, or 7-substitutions presents an outstanding opportunity to produce novel analogues of 1 by engineering NCS biosynthesis.
AB - The enediyne antitumor antibiotic neocarzinostatin (NCS) is produced by Streptomyces carzinostaticus ATCC15944. The biosynthetic pathway for the naphthoic acid moiety (boxed) of the NCS chromophore (1) is proposed to comprise five enzymes: NcsB, NcsB1, NcsB2, NcsB3, NcsB4. Both in vivo and in vitro experiments were used to support the proposed pathway. NcsB2 was characterized for the ability to catalyze the activation of 2-hydroxy-7-methoxy-5-methyl-1-naphthoic acid (3) via a naphthoyl-AMP ester (5) and subsequent formation of the corresponding coenzyme A ester. The finding that NcsB2 exhibits promiscuous substrate specificity toward a diverse set of naphthoic acid analogues with 2-, 5-, or 7-substitutions presents an outstanding opportunity to produce novel analogues of 1 by engineering NCS biosynthesis.
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U2 - 10.1021/ja071886a
DO - 10.1021/ja071886a
M3 - Article
C2 - 17539640
AN - SCOPUS:34347223552
SN - 0002-7863
VL - 129
SP - 7728
EP - 7729
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 25
ER -