The role of acyl-coenzyme A carboxylase complex in lipstatin biosynthesis of Streptomyces toxytricini.
Streptomyces toxytricini produces lipstatin, a specific inhibitor of pancreatic lipase, which is derived from two fatty acid moieties with eight and 14 carbon atoms. The pccB gene locus in 10.6 kb fragment of S. toxytricini chromosomal DNA contains three genes for acyl-coenzyme A carboxylase (ACCase) complex accA3, pccB, and pccE that are presumed to be involved in secondary metabolism. The pccB gene encoding a beta subunit of ACCase [carboxyltransferase (CT)] was identified upstream of pccE gene for a small protein of epsilon subunit. The accA3 encoding the alpha subunit of ACCase [biotin carboxylase (BC)] was also identified downstream of pccB gene. When the pccB and pccE genes were inactivated by homologous recombination, the lipstatin production was reduced as much as 80%. In contrast, the accumulation of another compound, tetradeca-5.8-dienoic acid (the major lipstatin precursor), was 4.5-fold increased in disruptant compared with wild-type. It implies that PccB of S. toxytricini is involved in the activation of octanoic acid to hexylmalonic acid for lipstatin biosynthesis.
Demirev
Atanas V
AV
Faculty of Pharmacy, Yeungnam University, Gyongsan, 712-749, Korea.
Khanal
Anamika
A
Sedai
Bhishma R
BR
Lim
Si Kyu
SK
Na
Min Kyun
MK
Nam
Doo Hyun
DH
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D019735:Carbon-Carbon Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007783:Lactones / Q000378:metabolism*; D008969:Molecular Sequence Data; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013302:Streptomyces / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D007783:Lactones; D021122:Protein Subunits; C054164:lipstatin; D019735:Carbon-Carbon Ligases; C018757:acyl-CoA carboxylase