| RRC ID |
29078
|
| Author |
Austin MB, Saito T, Bowman ME, Haydock S, Kato A, Moore BS, Kay RR, Noel JP.
|
| Title |
Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase.
|
| Journal |
Nat Chem Biol
|
| Abstract |
Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two approximately 3,000-residue D. discoideum proteins, termed 'steely', as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis.
|
| Volume |
2(9)
|
| Pages |
494-502
|
| Published |
2006-9-1
|
| DOI |
10.1038/nchembio811
|
| PII |
nchembio811
|
| PMID |
16906151
|
| PMC |
PMC2864586
|
| MeSH |
Acyltransferases / chemistry
Acyltransferases / genetics
Acyltransferases / metabolism*
Amino Acid Sequence
Animals
Catalytic Domain
Cloning, Molecular
Crystallography, X-Ray
Dictyostelium* / enzymology
Dictyostelium* / genetics
Dictyostelium* / growth & development
Dictyostelium* / metabolism
Dimerization
Fatty Acid Synthases / chemistry
Fatty Acid Synthases / genetics
Fatty Acid Synthases / metabolism*
Hexanones / chemistry
Hexanones / metabolism*
Hydrocarbons, Chlorinated / chemistry
Hydrocarbons, Chlorinated / metabolism*
Models, Molecular
Molecular Sequence Data
Mutation
Protein Conformation
Protozoan Proteins / chemistry
Protozoan Proteins / genetics
Protozoan Proteins / metabolism*
Sequence Homology, Amino Acid
|
| IF |
12.587
|
| Times Cited |
88
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Cellular slime molds |
S90270 |
