PMID- 18223152
OWN - NLM
STAT- MEDLINE
DCOM- 20080307
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 5
DP  - 2008 Feb 5
TI  - A phosphopantetheinylating polyketide synthase producing a linear polyene to 
      initiate enediyne antitumor antibiotic biosynthesis.
PG  - 1460-5
LID - 10.1073/pnas.0711625105 [doi]
AB  - The enediynes, unified by their unique molecular architecture and mode of action, 
      represent some of the most potent anticancer drugs ever discovered. The 
      biosynthesis of the enediyne core has been predicted to be initiated by a 
      polyketide synthase (PKS) that is distinct from all known PKSs. Characterization 
      of the enediyne PKS involved in C-1027 (SgcE) and neocarzinostatin (NcsE) 
      biosynthesis has now revealed that (i) the PKSs contain a central acyl carrier 
      protein domain and C-terminal phosphopantetheinyl transferase domain; (ii) the 
      PKSs are functional in heterologous hosts, and coexpression with an enediyne 
      thioesterase gene produces the first isolable compound, 
      1,3,5,7,9,11,13-pentadecaheptaene, in enediyne core biosynthesis; and (iii) the 
      findings for SgcE and NcsE are likely shared among all nine-membered enediynes, 
      thereby supporting a common mechanism to initiate enediyne biosynthesis.
FAU - Zhang, Jian
AU  - Zhang J
AD  - Department of Chemistry, Division of Pharmaceutical Sciences, and University of 
      Wisconsin National Cooperative Drug Discovery Group, University of Wisconsin, 
      Madison, WI 53705, USA.
FAU - Van Lanen, Steven G
AU  - Van Lanen SG
FAU - Ju, Jianhua
AU  - Ju J
FAU - Liu, Wen
AU  - Liu W
FAU - Dorrestein, Pieter C
AU  - Dorrestein PC
FAU - Li, Wenli
AU  - Li W
FAU - Kelleher, Neil L
AU  - Kelleher NL
FAU - Shen, Ben
AU  - Shen B
LA  - eng
GR  - U19 CA113297/CA/NCI NIH HHS/United States
GR  - F32 CA105984/CA/NCI NIH HHS/United States
GR  - GM073323/GM/NIGMS NIH HHS/United States
GR  - F32 GM073323/GM/NIGMS NIH HHS/United States
GR  - GM067725/GM/NIGMS NIH HHS/United States
GR  - CA113297/CA/NCI NIH HHS/United States
GR  - CA1059845/CA/NCI NIH HHS/United States
GR  - R01 GM067725/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080125
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Acyl Carrier Protein)
RN  - 0 (Aminoglycosides)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Enediynes)
RN  - 0 (Polyenes)
RN  - 120177-69-7 (C 1027)
RN  - 19F5HK2737 (Pantothenic Acid)
RN  - 1SCE5NG3E8 (phosphopantothenic acid)
RN  - 79956-01-7 (Polyketide Synthases)
RN  - 9014-02-2 (Zinostatin)
SB  - IM
MH  - Acyl Carrier Protein/*chemistry/genetics
MH  - Amino Acid Sequence
MH  - Aminoglycosides/biosynthesis/chemistry
MH  - Antibiotics, Antineoplastic/*biosynthesis
MH  - Binding Sites
MH  - Computational Biology
MH  - Enediynes/chemistry/*metabolism
MH  - Molecular Sequence Data
MH  - Pantothenic Acid/analogs & derivatives/chemistry
MH  - Polyenes/*chemistry
MH  - Polyketide Synthases/*chemistry/genetics
MH  - Protein Structure, Tertiary
MH  - Zinostatin/biosynthesis/chemistry
PMC - PMC2234166
COIS- The authors declare no conflict of interest.
EDAT- 2008/01/29 09:00
MHDA- 2008/03/08 09:00
PMCR- 2008/08/05
CRDT- 2008/01/29 09:00
PHST- 2008/01/29 09:00 [pubmed]
PHST- 2008/03/08 09:00 [medline]
PHST- 2008/01/29 09:00 [entrez]
PHST- 2008/08/05 00:00 [pmc-release]
AID - 0711625105 [pii]
AID - 9121 [pii]
AID - 10.1073/pnas.0711625105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1460-5. doi: 10.1073/pnas.0711625105. 
      Epub 2008 Jan 25.