Pimelic acid, the first precursor of the Bacillus subtilis biotin synthesis pathway, exists as the free acid and is assembled by fatty acid synthesis.
Pimelic acid, the first precursor of the Bacillus subtilis biotin synthesis pathway, exists as the free acid and is assembled by fatty acid synthesis.
复制标题
DOI：
10.1111/mmi.13648
复制
发表时间：
2017-05
影响因子：
3.6
通讯作者：
Cronan JE
中科院分区：
文献类型：
--
作者：
Manandhar M;Cronan JE
生物素合成途径容易分为两个阶段，合成七碳α，ω-二羧酸庚二酸酯部分和组装稠合杂环。负责庚二酸部分合成的生物素途径基因在细菌中变化很大，而环合成基因是高度保守的。枯草芽孢杆菌似乎具有用于生成庚二酸中间体的冗余基因bioI和bioW。与以前的遗传研究一致，我们发现bioW的缺失导致生物素营养缺陷型表型，而bioI的缺失没有。BioW是将庚二酸转化为庚二酰辅酶A的庚二酰辅酶A合成酶。BioW对生物素合成的重要性表明，游离形式的庚二酸是生物素合成的中间体，尽管在E.杆菌由于庚二酸在枯草芽孢杆菌中的来源是未知的，我们进行了13 C-NMR研究，以破译其产生的途径。我们的数据提供了证据，自由庚二酸在生物素合成中的作用和庚二酸生产中的脂肪酸合成的参与。浅蓝菌素是一种关键脂肪酸延伸酶FabF的抑制剂，可显著降低B的生物素产量。枯草芽孢杆菌静息细胞，而具有浅蓝菌素抗性FabF突变体的菌株产生更多的生物素。此外，补充庚二酸完全恢复浅蓝菌素处理的细胞中的生物素生产。这些结果表明源自脂肪酸合成途径的庚二酸是B中生物素的真正前体。枯草杆菌。简要概述游离庚二酸是枯草杆菌生物素合成的关键中间体。标记和抑制剂研究表明，庚二酸是由脂肪酸合成途径。
Biotin synthetic pathways are readily separated into two stages, synthesis of the seven carbon α, ω-dicarboxylic acid pimelate moiety and assembly of the fused heterocyclic rings. The biotin pathway genes responsible for pimelate moiety synthesis vary widely among bacteria whereas the ring synthesis genes are highly conserved. Bacillus subtilis seems to have redundant genes, bioI and bioW, for generation of the pimelate intermediate. Largely consistent with previous genetic studies we found that deletion of bioW caused a biotin auxotrophic phenotype whereas deletion of bioI did not. BioW is a pimeloyl-CoA synthetase that converts pimelic acid to pimeloyl-CoA. The essentiality of BioW for biotin synthesis indicates that the free form of pimelic acid is an intermediate in biotin synthesis although this is not the case in E. coli. Since the origin of pimelic acid in Bacillus subtilis is unknown, we carried out 13C-NMR studies to decipher the pathway for its generation. Our data provided evidence for the role of free pimelate in biotin synthesis and the involvement of fatty acid synthesis in pimelate production. Cerulenin, an inhibitor of the key fatty acid elongation enzyme, FabF, markedly decreased biotin production by B. subtilis resting cells whereas a strain having a cerulenin-resistant FabF mutant produced more biotin. In addition, supplementation with pimelic acid fully restored biotin production in cerulenin-treated cells. These results indicate that pimelic acid originating from fatty acid synthesis pathway is a bona fide precursor of biotin in B. subtilis. Abbreviated Summary Free pimelic acid is a key intermediate of biotin synthesis in Bacillus subtilis. Labeling and inhibitor studies show that pimelic acid is made by the fatty acid synthetic pathway.