2012年5月11日星期五

Biotin and amino acids have impacts on lincomycin biosynthesis

Lincomycin is an efficient broad-spectrum antibiotic. In clinical trials, it is used for the treatment of diseases caused by the anti-gram-positive bacteria. Lincomycin A and lincomycin B have different pharmacological effects. The antibacterial activities of lincomycin B are weaker than lincomycin. But it has stronger toxic side effects. In Chinese market, the B content in the finished product must be less than 5%.
Lincomycin is lincosamides antibiotics, L-tyrosine and the pentose phosphate cycle intermediates condensation of the entire biosynthetic pathway, including two branches: one by the L tyrosine synthesis of C proline (PPL,), another sedum sugar phosphate constitutes α amine methylthio forest. The speculation lincomycin A biosynthetic pathway has been reported in the literature. And it is proposed that tyrosine is the main precursor of first branch.
D biotin is an essential growth factor for many micro-organisms. Biotin acetyl-CoA carboxylase, pyruvate carboxylase, propionyl CoA carboxylase and 3-methyl croton-CoA carboxylase coenzyme composition, its glucose metabolism, fatty acid metabolism and protein and amino acid metabolism have greater impact. L-amino acids has a very important role in growth and metabolism of microorganisms, one hand, they can be generated through deamination. Transamination reaction of substances have a stimulating effect on the growth of microorganisms, such as a branch of fatty acid, on the other hand, after decarboxylation and other multi-step reaction generate pyruvate, oxaloacetate, propionyl CoA and succinyl-CoA such as the strengthening effect of the citric acid cycle.
In low concentration range, lower the biotin concentration is, greater the predictive value will be. Between the biological potency the valine, glutamic acid and valine, leucine and tyrosine, it gas has a significant impact on the biological potency of positive synergies. Valine and methionine has impact on the biological potency of the antagonistic effects of high and low methionine concentration of valine concentration, predict the efficiency of higher value. Low concentrations of biotin Lim Streptomyces glucose metabolism, lipid metabolism and amino acid metabolism, the role; higher demand for forest Streptomyces glutamate may be due to their participation in more deamination and amino transfer reaction to generate more α-ketoglutarate and other intermediate products.
α-ketoglutarate and other intermediates of the citric acid cycle on the one hand strengthen the role, on the other hand the lincomycin generate rich intermediates; valine and leucine for the branch amino acids, their deamination can generate the branched-chain fatty acids, have a stimulating effect on the growth of the lim streptomyces. Cosmetic raw material tyrosine can increase the synthesis rate and yield of the Lincomycin A forest can amphotericin A synthesis of precursors, fill the desired amount of precursor; methionine go A Keeling amine methyl transfer reaction of methyl donor, the synthesis rate of its lincomycin may have greater restrictions on the role of valine lincomycin growth stimulating effect, the bacteria body growth and synthesis of lincomycin in a way that a mutual checks and balances, so that it reflects the performance of antagonism between methionine and valine.
The syntheses of lincomycin require a higher bacterial concentration. So in the medium, it should increase the valine concentration appropriately and reduce the concentration of methionine. In the chemical synthetic, the chain mold fermentation can be used in production of lincomycin. In the two-level factorial design experiments with biotin and amino acids, the scientists find out that there are 6 factors which have significant impacts on biological potency: D biotin, L glutamic acid, L valine, L-methionine, L leucine and L-tyrosine.
Source:http://www.cosprm.com