iScience
·
2023
·Vol. 26
·期 7
·107048-107048
·
IF 5.8
Li Li,Zuxian Xu,Ruipin Cao,Jiaxin Li,Chang-Jer Wu,Yinglu Wang,Hu Zhu
We investigated the influence of hydroxyl groups on the anti-quorum-sensing (anti-QS) and anti-biofilm activity of structurally similar cyclic dipeptides, namely cyclo( L -Pro- L -Tyr), cyclo( L -Hyp- L -Tyr), and cyclo( L -Pro- L -Phe), against Pseudomonas aeruginosa PAO1. Cyclo( L -Pro- L -Phe), lacking hydroxyl groups, displayed higher virulence factor inhibition and cytotoxicity, but showed less inhibitory ability in biofilm formation. Cyclo( L -Pro- L -Tyr) and cyclo( L -Hyp- L -Tyr) suppressed genes in both the las and rh l systems, whereas cyclo( L -Pro- L -Phe) mainly downregulated rhl I and pqs R expression. These cyclic dipeptides interacted with the QS-related protein LasR, with similar binding efficiency to the autoinducer 3OC12-HSL, except for cyclo( L -Pro- L -Phe) which had lower affinity. In addition, the introduction of hydroxyl groups significantly improved the self-assembly ability of these peptides. Both cyclo( L -Pro- L -Tyr) and cyclo( L -Hyp- L -Tyr) formed assembly particles at the highest tested concentration. The findings revealed the structure-function relationship of this kind of cyclic dipeptides and provided basis for our follow-up research in the design and modification of anti-QS compounds.
研究领域:
微生物学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMBIOCHEM
·
2024
·
IF 2.6
Dan Li,Yi Wang,Yuanyuan Xu,Hongping Long,Wenqing Min,Shangfeng Gao,Shu-Ming Li,Xia Yu
Graphical The F253G mutation of CdpC3PT exhibited enhanced catalytic efficiency in geranylation of cyclic dipeptides and naphthols. The mutant's reaction specificity is towards C7-geranylation of cyclic dipeptides, while 1-naphthol and its derivatives were converted into C4-geranylated products. Furthermore, five geranylated products ( 2G1 and 4G1 – 7G1 ) displayed antibacterial activity against Bacillus subtilis , with MIC values ranging from 4 to 32 μg/mL, surpassing their non-geranylated precursors. This research broadens the range of geranyl-modifying biocatalysts and highlights the potential for developing efficient or functionally modified biocatalysts. Prenyl modification often improves the biological activities of compounds. Prenyltransferases have attracted attention as environmentally friendly biocatalysts for catalyzing prenyl modification of compounds. Compared to dimethylallyl modifications, research on geranyl modifications is relatively limited. To enrich biocatalytic toolboxes for generating potentially bioactive geranylated derivatives, this study developed methodologies to synthesize two types of geranylated compounds, i. e ., geranylated tryptophan-containing cyclic dipeptides and geranylated naphthols, employing the F253G mutant of CdpC3PT, a cyclic dipeptide prenyltransferase from Neosartorya fischeri . The cyclic dipeptides ( 1 – 3 ) were transformed into C7-geranylated products ( 1G1 – 3G1 ), whereas 1-naphthol ( 4 ) and derivatives ( 5 – 6 ) yielded C4-geranylated products ( 4G1 – 6G1 ) and 2,7-dihydroxynaphthalene ( 7 ) generated a C3-geranylated product ( 7G1 ). All seven substrates and their geranylated products underwent antibacterial efficacy testing against Bacillus subtilis . Among them, five geranylated compounds ( 2G1 and 4G1 – 7G1 ) demonstrated antibacterial efficacies against Bacillus subtilis , with MIC values ranging from 4 to 32 μg/mL, surpassing their non-geranylated precursors. This research broadens the tools of geranyl-modifying biocatalysts, illustrates a case for developing highly efficient or function-altered biocatalysts and showcases the potential of prenyltransferases in the biosynthesis of bioactive small molecules.
研究领域:
生物化学
·
微生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
AMB Express
·
2018
·Vol. 8
·期 1
·1-13
·
IF 1.719
Liang Jibei,Cheng Tao,Huang Yi,Liu Jianhua
Enhanced bioremediation is a favorable approach for petroleum pollutant cleanup, which depends on the growth of oil-eating microorganisms. In this study, we show that, by using the modified T-RFLP (mT-RFLP) methodology, one of the four major microbial populations derived from oil sludge has failed to propagate in MS medium supplemented with 2% yeast extract (YE). rDNA sequence-based analysis indicated that the four populations were Donghicola sp. CT5, Bacillus sp. CT6, Alcaligenes sp. CT10, and Pseudomonas sp. ZS1. Four purified strains grow well individually in MS medium supplemented with 2% YE, suggesting that ZS1 growth is antagonized by other strains. Co-growth analysis using mT-RFLP methodology and plate inhibitory assay indicated that ZS1 exhibited antagonistic effect against CT5 and CT6. On the other hand, co-growth analysis and plate inhibition assay showed that CT10 antagonized against ZS1. To investigate the potential compounds responsible for the antagonism, supernatant of CT10 culture was subjected to GC–MS analysis. Analysis indicated that CT10 produced a number of antimicrobial compounds including cyclodipeptide c-(L-Pro-L-Phe), which was known to inhibit the growth of Pseudomonas sp. Growth test using the purified c-(L-Pro-L-Phe) from CT10 confirmed its inhibitory activity. We further showed that, using both gravimetric and GC analysis, CT10 antagonism against the oil-eating ZS1 led to the diminishing of crude oil degradation. Together, our results indicate that bioremediation can be affected by environmental antagonists.
研究领域:
微生物学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF PHARMACAL RESEARCH
·
2016
·Vol. 39
·期 6
·762-770
·
IF 2.49
Wang Nan,Cui Cheng-Bin,Li Chang-Wei
A novel cyclic dipeptide, named penicimutide ( 1 ), and four known cyclic dipeptides, cyclo( l -Val- l -Pro) ( 2 ), cyclo( l -Ile- l -Pro) ( 3 ), cyclo( l -Leu- l -Pro) ( 4 ) and cyclo( l -Phe- l -Pro) ( 5 ), were isolated from a neomycin-resistant mutant of the marine-derived fungus Penicillium
purpurogenum G59. The structure of 1 , including the absolute configuration, was determined by spectroscopic and chemical methods, especially NMR and Marfey’s analysis. An unusual amino acid in 1 , 4,5-didehydro- l -leucine, was found for the first time occurring in nature. HPLC–ESI–MS analysis evidenced that 1 – 3 were produced only in the mutant strain, but 4 and 5 were produced in both the mutant and parental strains, indicating that the introduction of neomycin-resistance in the mutant activated pathways of 1 – 3 biosynthesis that were silent in the parental strain. Compound 1 selectively inhibited HeLa cells (among five tested human cancer cell lines) with an inhibition rate (IR %) of 39.4 % at 100 µg/mL, a similar inhibition intensity to that of the positive control 5-fluorouracil (IR % of 41.4 % at 100 µg/mL against HeLa cells). The present work exemplifies the effectiveness of our previous DMSO-mediated method for introducing drug-resistance in fungi to activate silent biosynthetic pathways to obtain new bioactive compounds.
研究领域:
微生物学
·
药物化学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2022
·
IF 12.545
Xuecheng Zhu,Ying Zhang,Luxuan Han,Huilin Liu,Baoguo Sun
Quantum confinement (QC) effect-related materials have been extensively studied as photoluminescent probes for agricultural, food, and environmental analyses, with the advantage of simple-to-synthesize, reusable, nontoxic, and environmentally friendly. Herein, we propose a strategy to dimerize aromatic cyclo-dipeptides, namely cyclo-ditryptophan (cyclo-WW), cyclo-diphenylalanine (cyclo-FF), and cyclo-dihistidine (cyclo-HH), into quantum dots as basic building blocks for the self-assembly of QC supramolecular structures with excellent photoluminescent properties in aqueous solutions. In particular, through coordination with Zn(II), the bandgap can be tuned to change the photo-absorption and luminescence properties of the cyclo-dipeptide-based QC assemblies. The fluorescence quantum yield of cyclo-WW+Zn(II) was 16.9%. Such a good luminous effect makes it applicable to the detection of LC . A good linear relationship between fluorescence response of cyclo-WW+Zn(II) and LC concentration was observed in the range of 5–350 μg/L, with a low limit of detection of 2.9 μg/L and good spiked recovery of 90.72%–104.3%. A visual platform using the cyclo-WW+Zn(II)-based photoluminescent hydrogel and smartphone-assisted sample-to-answer analyzer were developed, which showed good responsiveness to LC. The developed fluorescence method , validated using traditional HPLC, is a biocompatible alternative for the rapid detection of trace pollutants with the advantages of portability and simple operation.
研究领域:
分析化学
·
环境科学
·
材料科学
✓ 已验证
DOI
高影响因子
Marine Drugs
·
2022
·Vol. 20
·期 2
·85
·
IF 6.085
Yinglu Wang,Qian Zheng,Li Li,Lile Pan,Hu Zhu
Quorum sensing (QS) can regulate the pathogenicity of bacteria and the production of some virulence factors. It is a promising target for screening to find anti-virulence agents in the coming post-antibiotics era. Cyclo (L-Trp-L-Ser), one variety of cyclic dipeptides (CDPs), isolated from a marine bacteriumRheinheimera aquimaris, exhibited anti-QS activity againstChromobacterium violaceumCV026 andPseudomonas aeruginosaPAO1. Unlike the CDPs composed of phenylalanine or tyrosine, the anti-QS activity has been widely studied; however, cyclo (L-Trp-L-Ser) and derivatives, containing one tryptophan unit and one non-aromatic amino acid, have not been systematically explored. Herein, the cyclo (L-Trp-L-Ser) and seven derivatives were synthesized and evaluated. All tryptophane-contained CDPs were able to decrease the production of violacein inC.violaceumCV026 and predicted as binding within the same pocket of receptor protein CviR, but in lower binding energy compared with the natural ligand C6HSL. As forP. aeruginosaPAO1, owning more complicated QS systems, these CDPs also exhibited inhibitory effects on pyocyanin production, swimming motility, biofilm formation, and adhesion. These investigations suggested a promising way to keep the tryptophan untouched and make modifications on the non-aromatic unit to increase the anti-QS activity and decrease the cytotoxicity, thus developing a novel CDP-based anti-virulence agent.Keywords:anti-quorum sensing;cyclic dipeptides;tryptophane;Pseudomonas aeruginosa;biofilm;bacterial adhesion
研究领域:
微生物学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）