TY - JOUR
T1 - Biosynthesis of the β-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring β-amino acyl-S-carrier protein intermediates
AU - Van Lanen, Steven G.
AU - Dorrestein, Pieter C.
AU - Christenson, Steve D.
AU - Liu, Wen
AU - Ju, Jianhua
AU - Kelleher, Neil L.
AU - Shen, Ben
PY - 2005/8/24
Y1 - 2005/8/24
N2 - The enediyne antitumor antibiotic C-1027 chromoprotein is produced by Streptomyces globisporus. The biosynthesis of the (S)-3-chloro-4,5-dihydroxy-β-phenylalanine moiety (boxed) of the C-1027 chromophore (1) from l-tyrosine (3) and its incorporation into 1 are catalyzed by six enzymes: SgcC, SgcC1, SgcC2, SgcC3, SgcC4, ShcC5. In vivo and in vitro characterization of these enzymes delineated this pathway, unveiling a novel strategy for β-amino acid modification featuring β-amino acyl-S-carrier protein intermediates. These findings shed new light into β-amino acid biosynthesis and present a new opportunity to engineer the C-1027 biosynthetic machinery for the production of novel analogues as exemplified by 20-deschloro-C-1027 (4), 20-deschro-22-deshydroxy-C-1027 (5), and 22-deshydroxy-C-1027 (6).
AB - The enediyne antitumor antibiotic C-1027 chromoprotein is produced by Streptomyces globisporus. The biosynthesis of the (S)-3-chloro-4,5-dihydroxy-β-phenylalanine moiety (boxed) of the C-1027 chromophore (1) from l-tyrosine (3) and its incorporation into 1 are catalyzed by six enzymes: SgcC, SgcC1, SgcC2, SgcC3, SgcC4, ShcC5. In vivo and in vitro characterization of these enzymes delineated this pathway, unveiling a novel strategy for β-amino acid modification featuring β-amino acyl-S-carrier protein intermediates. These findings shed new light into β-amino acid biosynthesis and present a new opportunity to engineer the C-1027 biosynthetic machinery for the production of novel analogues as exemplified by 20-deschloro-C-1027 (4), 20-deschro-22-deshydroxy-C-1027 (5), and 22-deshydroxy-C-1027 (6).
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U2 - 10.1021/ja052871k
DO - 10.1021/ja052871k
M3 - Article
C2 - 16104723
AN - SCOPUS:23944436899
SN - 0002-7863
VL - 127
SP - 11594
EP - 11595
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 33
ER -