Faculty of Pharmacy, Yeungnam University, Gyongsan, 712-749, Korea.
Appl Microbiol Biotechnol. 2010 Jul;87(3):1129-39. doi: 10.1007/s00253-010-2587-2. Epub 2010 May 2.
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.
土霉素链霉菌产生脂酶抑制剂，一种胰腺脂酶的特异性抑制剂，来源于具有 8 个和 14 个碳原子的两个脂肪酸部分。10.6kb 片段的 pccB 基因座在土霉素链霉菌染色体 DNA 中包含三个酰基辅酶 A 羧化酶（ACCase）复合物 accA3、pccB 和 pccE 的基因，据推测它们参与了次级代谢。pccB 基因编码 ACCase 的β亚基[羧基转移酶（CT）]，位于 pccE 基因编码的ε亚基小蛋白之前。accA3 编码 ACCase 的α亚基[生物素羧化酶（BC）]，也位于 pccB 基因的下游。当 pccB 和 pccE 基因通过同源重组失活时，脂酶抑制剂的产量减少了 80%。相比之下，与野生型相比，突变体中另一种化合物十四碳-5,8-二烯酸（脂酶抑制剂的主要前体）的积累增加了 4.5 倍。这表明土霉素链霉菌的 PccB 参与了将辛酸激活为己基丙二酸，用于脂酶抑制剂的生物合成。
