PMID- 18252726
OWN - NLM
STAT- MEDLINE
DCOM- 20080619
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 17
DP  - 2008 Apr 25
TI  - Dissecting the functional role of polyketide synthases in Dictyostelium 
      discoideum: biosynthesis of the differentiation regulating factor 
      4-methyl-5-pentylbenzene-1,3-diol.
PG  - 11348-54
LID - 10.1074/jbc.M709588200 [doi]
AB  - Dictyostelium discoideum exhibits the largest repository of polyketide synthase 
      (PKS) proteins of all known genomes. However, the functional relevance of these 
      proteins in the biology of this organism remains largely obscure. On the basis of 
      computational, biochemical, and gene expression studies, we propose that the 
      multifunctional Dictyostelium PKS (DiPKS) protein DiPKS1 could be involved in the 
      biosynthesis of the differentiation regulating factor 
      4-methyl-5-pentylbenzene-1,3-diol (MPBD). Our cell-free reconstitution studies of 
      a novel acyl carrier protein Type III PKS didomain from DiPKS1 revealed a crucial 
      role of protein-protein interactions in determining the final biosynthetic 
      product. Whereas the Type III PKS domain by itself primarily produces acyl 
      pyrones, the presence of the interacting acyl carrier protein domain modulates 
      the catalytic activity to produce the alkyl resorcinol scaffold of MPBD. 
      Furthermore, we have characterized an O-methyltransferase (OMT12) from 
      Dictyostelium with the capability to modify this resorcinol ring to synthesize a 
      variant of MPBD. We propose that such a modification in vivo could in fact 
      provide subtle variations in biological function and specificity. In addition, we 
      have performed systematic computational analysis of 45 multidomain PKSs, which 
      revealed several unique features in DiPKS proteins. Our studies provide a new 
      perspective in understanding mechanisms by which metabolic diversity could be 
      generated by combining existing functional scaffolds.
FAU - Ghosh, Ratna
AU  - Ghosh R
AD  - National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
FAU - Chhabra, Arush
AU  - Chhabra A
FAU - Phatale, Pallavi A
AU  - Phatale PA
FAU - Samrat, Subodh K
AU  - Samrat SK
FAU - Sharma, Jyoti
AU  - Sharma J
FAU - Gosain, Anuradha
AU  - Gosain A
FAU - Mohanty, Debasisa
AU  - Mohanty D
FAU - Saran, Shweta
AU  - Saran S
FAU - Gokhale, Rajesh S
AU  - Gokhale RS
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080205
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (4-methyl-5-pentylbenzene-1,3-diol)
RN  - 0 (Resorcinols)
RN  - 79956-01-7 (Polyketide Synthases)
RN  - EC 2.1.1.- (Methyltransferases)
SB  - IM
MH  - Animals
MH  - Cell-Free System
MH  - Computational Biology
MH  - Dictyostelium/*enzymology
MH  - *Gene Expression Regulation, Enzymologic
MH  - Kinetics
MH  - Methyltransferases/metabolism
MH  - Models, Biological
MH  - Models, Chemical
MH  - Phylogeny
MH  - Polyketide Synthases/*metabolism
MH  - Protein Conformation
MH  - Protein Structure, Tertiary
MH  - Resorcinols/*metabolism
MH  - Software
EDAT- 2008/02/07 09:00
MHDA- 2008/06/20 09:00
CRDT- 2008/02/07 09:00
PHST- 2008/02/07 09:00 [pubmed]
PHST- 2008/06/20 09:00 [medline]
PHST- 2008/02/07 09:00 [entrez]
AID - S0021-9258(20)61926-3 [pii]
AID - 10.1074/jbc.M709588200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Apr 25;283(17):11348-54. doi: 10.1074/jbc.M709588200. Epub 2008 
      Feb 5.