JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Shuangshuang Zhao,Cheng Xiao,Jiajie Wang,Kailin Tian,Wenxia Ji,Tingting Yang,Babar Khan,Guoliang Qian,Wei Yan,Yonghao Ye
β-Ketoacyl-acyl carrier protein synthase III (KAS III, FabH) is essential for bacterial fatty acid biosynthesis. Recent studies indicate that FabH can be a potential target for bactericide development. In the present study, an immobilized FabH column was developed and used to screen FabH inhibitors from complex natural product extracts. Combined with HPLC, four secondary metabolites, alternariol (1), altenuisol (2), alterlactone (3), and dehydroaltenusin (4), were site-directed, isolated, and identified from the crude extract of Alternaria alternata ZHJG5. These compounds showed inhibitory activities on FabH of Xanthomonas oryzae pv. oryzae (Xoo) with IC50 values from 29.5 to 74.1 μM and also displayed a varying degree of antibacterial activities against Xoo with minimal inhibitory concentration values from 4 to 64 μg/mL. Molecular modeling was then used to picture how the compounds interact with XooFabH. Two inhibitors, compounds 1 and 3, exhibited significant bactericidal activity against rice bacterial leaf blight with a protective efficiency of 66.2 and 82.5% at the concentration of 200 μg/mL, respectively, suggesting that they could be lead candidates to develop novel bactericides.
研究领域:
微生物学
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药理学
·
植物病理学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
·
2016
·Vol. 43
·期 4
·557-566
·
IF 2.745
Cao Weijia,Ma Weichao,Zhang Bowen,Wang Xin,Chen Kequan,Li Yan,Ouyang Pingkai
The development of efficient microbial processes for pinocembrin production has attracted considerable attention. However, pinocembrin biosynthetic efficiency is greatly limited by the low availability of the malonyl-CoA cofactor in Escherichia coli. Fatty acid biosynthesis is the only metabolic process in E. coli that consumes malonyl-CoA; therefore, we overexpressed the fatty acid biosynthetic pathway enzymes β-ketoacyl-ACP synthase III (FabH) and β-ketoacyl-ACP synthase II (FabF) alone and in combination, and investigated the effect on malonyl-CoA. Interestingly, overexpressing FabH, FabF or both enzymes in E. coli BL21 (DE3) decreased fatty acid synthesis and increased cellular malonyl-CoA levels 1.4-, 1.6-, and 1.2-fold, respectively. Furthermore, pinocembrin production was increased 10.6-, 31.8-, and 5.87-fold in recombinant strains overexpressing FabH, FabF and both enzymes, respectively. Overexpression of FabF, therefore, triggered the highest pinocembrin production and malonyl-CoA levels. The addition of cerulenin further increased pinocembrin production in the FabF-overexpressing strain, from 25.8 to 29.9 mg/L. These results demonstrated that overexpressing fatty acid synthases can increase malonyl-CoA availability and improve pinocembrin production in a recombinant E. coli host. This strategy may hold promise for the production of other important natural products in which cellular malonyl-CoA is rate limiting.
研究领域:
合成生物学
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代谢工程
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIV DER PHARMAZIE
·
2020
·Vol. 354
·期 2
·2000165
·
IF 2.59
Yushan Huang,Hongmei Hu,Rui Yan,Liwen Lin,Mingxia Song,Xiaodong Yao
A series of 3-phenyl-1-phenylsulfonyl pyrazoles containing an aminoguanidine moiety was designed, synthesized, and evaluated for their antimicrobial and anticancer activities. The majority of the target compounds showed broad-spectrum antimicrobial activity against the tested strains, with minimum inhibitory concentration (MIC) values ranging from 2 to 64 μg/ml. Compound 5k , showing the most potent antimicrobial activity against Bacillus subtilis CMCC 63501 and multidrug-resistant Staphylococcus aureus ATCC 43300 with an MIC value of 2 μg/ml, was the most promising one in this series. It was also effective for S. aureus ATCC 33591 and multidrug-resistant Escherichia coli ATCC BAA-196 at higher concentrations. The bactericidal time–kill kinetics test illustrated that compound 5k had rapid bactericidal potential. Docking results exhibited that compound 5k showed various kinds of binding to the FabH receptor, reflecting that 5k could bind with the active site well. All compounds showed excellent activity against the investigated cancer cells, with IC 50 values ranging from 1.90 to 54.53 µM. Among them, compound 5f showed prominent cytotoxicity with IC 50 = 1.90 µM against A549 cells, while exhibiting lower inhibitory activity against 293T cells (IC 50 = 41.72 µM), indicating that it has the potential for a good therapeutic index as an anticancer drug.
研究领域:
药物化学
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微生物学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
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