1.Biosynthesis-based production improvement and structure modification of erythromycin A.
Dandan CHEN ; Jiequn WU ; Wen LIU
Chinese Journal of Biotechnology 2015;31(6):939-954
Erythromycin A is a clinically important macrolide antibiotic with broad-spectrum activity. Its biosynthesis involves the formation of the 14-membered skeleton catalyzed by polyketide synthases, and the modification steps such as hydroxylation, glycosylation and methylation. Based on the understanding of the biosynthetic mechanism, it is reliable to genetically manipulate the erythromycin A-producing strain for production improvement and structure modification. In this paper, we reviewed the progress regarding erythromycin A in high-producing strain construction and chemical structure derivation, to provide insights for further development.
Anti-Bacterial Agents
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biosynthesis
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chemistry
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Erythromycin
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biosynthesis
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chemistry
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Glycosylation
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Hydroxylation
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Methylation
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Multigene Family
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Polyketide Synthases
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metabolism
2.A relationship between arsenite sodium, arsenate sodium metabolites and related metabolic enzymes in rat kidney
Huimin YU ; Qian WANG ; Rongxiang XIA ; Jiequn WEI ; Jun WU ; Yujian ZHENG
Chinese Journal of Endemiology 2014;33(2):150-154
Objective To investigate the relationship between metabolites of sodium arsenite and sodium dihydrogen arsenate with related metabolic enzymes in kidney of male rats.Methods According to body mass,thirty-five male Wistar rats(body mass 150-190 g) were divided into 7 groups by random number table.Control group drank deionized water; the contents of iAsⅢ in low,medium and high arsenite groups and the contents of iAsv in low,medium and high of sodium dihydrogen arsenate groups were 2.2,6.7 and 20.0 mg/kg,respectively.After 3 months,kidneys were collected and stored at-80 C; high performance liquid chromatography and hydride genesis atomic fluorescence spectroscopy (HPLC-HGAFS) was used to determine the level of arsenic metabolites in kidney,and enzyme-linked immunosorbent assay was used to detect and analyze the content or the activity of metabolic enzymes,meanwhile correlation studies between the level of metabolites and the activity of metabolic enzymes were carried out.Results The differences of total arsenic (TAs),dimethyl arsenic acid (DMA),monomethyl arsenic acid (MMA) and methyl transferase enzyme activity in kidneys of rats between groups were statistically significant (F =1874.672,H =33.513,31.002,F =79.607,all P < 0.01).The TAs[(526.52 ± 25.56),(1 654.00 ± 101.55),(1 904.24 ± 104.76)μg,/kg] and DMA[(323.20 + 16.13),(1 444.40 ± 113.81),(1 765.40 ± 104.39)μg/kg] of sodium arsenite in low,medium and high dose groups were higher than those of the corresponding sodium dihydrogen arsenate groups [(235.70 ± 6.23),(471.05 ± 18.32),(1 677.40 ± 83.29)μg/kg,and(0.00 ± 0.00),(1.75 ± 0.16),(410.50 ± 19.76)μg/kg,P < 0.0024 or < 0.05] ; the MMA[(4.02 + 0.86),(4.20 ± 0.65),(4.04 ± 0.80)μg/kg] of sodium arsenite in low,medium and high dose groups were lower than those of the corresponding sodium dihydrogen arsenate groups[(98.90 ± 9.59),(376.50 ± 15.41),(1 131.90 ± 74.26) μg/kg,all P< 0.05]; the methyl transferase enzyme activities[(7.80 ± 0.93),(5.55 ± 0.49),(3.56 ± 0.26)U/g] of sodium arsenite in low,medium and high dose groups were lower than those of the corresponding sodium dihydrogen arsenate group[(11.59 ± 0.93),(8.93 ± 0.88),(6.52 ± 1.04)U/g,all P < 0.0024].The DMA of sodium arsenite in low,medium and high dose groups,the MMA of sodium dihydrogen arsenate in medium and high dose groups were positively correlated with those of TAs in each group(r =0.970,0.984,0.997,0.947,0.961,all P < 0.05).Conclusions Effects of sodium arsenite and sodium dihydrogen arsenate on arsenic metobdites and related metabolic enzymes in kidney of rats are different.The function of sodium dihydrogen arsenate in promoting methyl transferase activity is stronger than that of sodium arsenite,which affects the amount and distribution of arsenic methylation metabolites in kidney.
3.Research progress on indanomycin natural products
Yuqin ZHU ; Jiequn WU ; Peng SUN
Journal of Pharmaceutical Practice 2020;38(3):211-215
Indanomycins are a class of secondary metabolites of microorganisms with a trans-tetrahydroindan (indane) ring. These compounds generally have good antibacterial, insecticidal and antitumor biological activities, which have caused wide interest for medicinal chemists and biologists. This review summarizes the research progress of the discovery, biological activity, chemical synthesis and biosynthesis of indanomycin compounds since 1979 and provides scientific reference for the research and development of indanomycin antibiotics.