Applied Microbial and Cell Physiology

Applied Microbiology and Biotechnology

, Volume 87, Issue 3, pp 1129-1139

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

The role of acyl-coenzyme A carboxylase complex in lipstatin biosynthesis of Streptomyces toxytricini

  • Atanas V. DemirevAffiliated withFaculty of Pharmacy, Yeungnam University
  • , Anamika KhanalAffiliated withFaculty of Pharmacy, Yeungnam University
  • , Bhishma R. SedaiAffiliated withFaculty of Pharmacy, Yeungnam University
  • , Si Kyu LimAffiliated withGenoTech Corporation
  • , Min Kyun NaAffiliated withFaculty of Pharmacy, Yeungnam University
  • , Doo Hyun NamAffiliated withFaculty of Pharmacy, Yeungnam University Email author 


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 β subunit of ACCase [carboxyltransferase (CT)] was identified upstream of pccE gene for a small protein of ε subunit. The accA3 encoding the α 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.


Acyl-CoA carboxylase pccB Lipstatin Octanoic acid Tetradeca-5.8-dienoic acid Streptomyces toxytricini