Banca de DEFESA: CLARA DETULIO MARTINS CAVALCANTE

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : CLARA DETULIO MARTINS CAVALCANTE
DATE: 22/08/2025
TIME: 14:00
LOCAL: videoconferência
TITLE:

GENOMIC AND METABOLOMIC PROPECTING OF ANTIMICROBIAL MOLECULES FROM Bacillus spp.

KEY WORDS:

Bacillus spp.; Antimicrobial Peptides; Genome Mining; Metabolomic; Antimicrobial Resistance

PAGES: 114
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Química dos Produtos Naturais
SUMMARY:

Antimicrobial resistance represents one of the main threats to global public health, driving the search for new antimicrobial compounds. Since the discovery of penicillin, microbial natural products have been consolidated as one of the main sources of antibiotics. In this context, bacteria of the genus Bacillus have been widely studied for their ability to produce peptides with antimicrobial activity. In this study, eighteen strains of Bacillus spp. were isolated from oil-contaminated sand sediments and from wastewater from onshore and offshore oil wells. These strains were investigated for their biosynthetic potential through integrated genome mining and metabolomic approaches, aiming the discovery of new antimicrobials. Genome analysis using the AntiSMASH tool resulted in the annotation of biosynthetic gene clusters, predominantly classified within the structural classes of nonribosomal peptides, terpenes, and polyketides. The strain Bacillus paralicheniformis BD165 was selected for cultivation in MRS medium supplemented with 10% maltose for 48 h. Extracts were obtained through liquid–liquid extraction with ethyl acetate and butanol, followed by chromatographic fractionation and characterization by mass spectrometry and nuclear magnetic resonance (NMR). UPLC-QTOF-MS/MS analyses revealed the presence of cyclic peptides consistent with bioactive compounds previously described in the literature, including cyclo(Pro–Val), cyclo(Pro–Leu), cyclo(Pro–Phe), cyclo(Leu–Leu), cyclo(Leu)₄, and cyclo(Leu)₆. Fractions selected based on their H1 NMR chemical profile were subjected to one- and two-dimensional NMR experiments, allowing partial structural characterization of the compounds, with results consistent with the annotations obtained by mass spectrometry. In silico toxicity prediction indicated a low toxic potential for leucine-derived compounds, and a gradual increase in toxicity for structures containing proline and phenylalanine. Molecular docking studies demonstrated higher binding affinities of cyclo(Leu)₆ and its isomer, thermoactinoamide J, with the proteins AdeG (−11,1 kcal/mol), TolC (−9,6 kcal/mol), and OmpK36 (−10,4 kcal/mol), all associated with resistance in Gram-negative bacteria. The dataset obtained reinforces the chemical and biological potential of B. paralicheniformis and contributes to filling the gap of underrepresented spectral information in public databases. The results establish a solid foundation for the characterization of peptides produced by Bacillus spp. and guide future in vitro bioassays with isolated compounds.

COMMITTEE MEMBERS:
Externa à Instituição - ARIANA AZEVEDO VASCONCELOS - UFRJ
Interno - 2276354 - LEANDRO DE SANTIS FERREIRA
Externa à Instituição - PATRICIA SARTORELLI - UNIFESP
Presidente - 1569526 - RENATA MENDONÇA ARAUJO