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Cyclo(L-Leucyl-L-Prolyl) from Lactobacillus coryniformis BCH-4 inhibits the proliferation of Aspergillus flavus: an in vitro to in silico approach

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Abstract

Fungal spoilage led to a considerable economic loss of foodstuff which ultimately affects public health due to mycotoxins production. Moreover, the consumption of commercial antifungal drugs creates side effects and develops antifungal resistance. To overcome these challenges, the current work was aimed to investigate novel antifungal cyclic dipeptide (CDP) from Lactobacillus coryniformis (Loigolactobacillus coryniformis) BCH-4. CDPs have flexible, cyclic, and stable conformation. The proline-based CDPs provide additional structural compatibility and bio-functional values. Keeping in view, high-performance liquid chromatography (HPLC) was performed to explore cyclo(L-Leu-L-Pro) from L. coryniformis BCH-4. The HPLC detected concentration (135 ± 7.07 mg/mL) exhibited in vitro antifungal activity of 5.66 ± 0.57 mm (inhibitory zone) against Aspergillus flavus. Based on these results, cyclo(L-Leu-L-Pro) was used as a bioprotectant for selected food samples (grapes, lemon, cashew nuts, and almonds). A significant impact of cyclo(L-Leu-L-Pro) was observed in contrast with MRS broth (control) and cell-free supernatant. In silico molecular docking analysis of this CDP was carried out against FAD glucose dehydrogenase, dihydrofolate reductase, and urate oxidase of A. flavus as target proteins. Among these proteins, FAD glucose dehydrogenase exerted strong interactions with cyclo(L-Leu-L-Pro) having S-score of  – 8.21. The results evaluated that the detected CDP has strong interactions with selected proteins, causing excellent growth inhibition of A. flavus. Therefore, cyclo(L-Leu-L-Pro) could be used as a potent bioprotectant against food-borne pathogenic fungi.

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Abbreviations

A. flavus :

Aspergillus flavus

CDPs:

Cyclic dipeptides

CFS:

Cell-free supernatant

DHFR:

Dihydrofolate reductase

DKP:

2,5-Diketopiperazines

FAD:

Flavin adenine dinucleotide

GRAS:

Generally recognized as safe

L. coryniformis :

Lactobacillus coryniformis

LAB:

Lactic acid bacteria

MOE:

Molecular operating environment

RMSD:

Root mean squared deviation

THF:

Tetrahydro-folic acid

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Funding

This study was funded by Higher Education Commission, Pakistan under Government College University Faisalabad-Research Support Program (GCUF-RSP), award letter no. GCUF/Reg/17/3655 and project code: 19-ACH-19.

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Authors and Affiliations

  1. Department of Biochemistry, Government College University, Faisalabad, Pakistan

    Mahwish Salman, Anam Tariq & Ghulam Mustafa

  2. Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan

    Muhammad Rizwan Javed

  3. Department of Chemistry, Government College University, Faisalabad, Pakistan

    Shazia Naheed

  4. State Key Laboratory of Bioreactor Engineering and School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China

    Sarmad Ahmad Qamar

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  1. Mahwish Salman
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  2. Anam Tariq
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  3. Ghulam Mustafa
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  5. Shazia Naheed
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  6. Sarmad Ahmad Qamar
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Correspondence to Mahwish Salman or Sarmad Ahmad Qamar.

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Communicated by Erko Stackebrandt.

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Salman, M., Tariq, A., Mustafa, G. et al. Cyclo(L-Leucyl-L-Prolyl) from Lactobacillus coryniformis BCH-4 inhibits the proliferation of Aspergillus flavus: an in vitro to in silico approach. Arch Microbiol 204, 267 (2022). https://doi.org/10.1007/s00203-022-02884-z

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