dc.description.abstract |
Antibiotics have played a crucial role in modern medicine for more than 60 years by effectively
treating infectious diseases and reducing the occurrence of infections in immunocompromised
patients. Nevertheless, the excessive use of antibiotics has resulted in an increase in
antibiotic-resistant bacteria, requiring the development of new antibiotics with unique
mechanisms. One promising approach is exploring natural products such as fungal secondary
metabolites. Precursor-directed biosynthesis (PDB) involves the use of specific precursor
molecules to produce modified metabolites possessing unique activities, potentially useful in
medicine, agriculture, and other fields.
PDB uses the adaptive metabolic processes of microorganisms to incorporate unnatural
precursors, creating novel derivatives with potentially improved efficacy and reduced toxicity.
This approach requires understanding microbial growth, precursor behaviour, and biosynthetic
pathways. Advances in synthetic biology and metabolic engineering have further expanded
these possibilities.
Aspergillus species, commonly found fungi, can exhibit both advantageous and detrimental
effects. Certain species can cause infections and producing harmful mycotoxins, whereas
Aspergillus terreus is known for its ability to thrive in adverse conditions and produce beneficial
secondary metabolites, including lovastatin (a cholesterol-lowering drug) and antibacterial
agents like terretonin.
In this study, the incorporation of phenylalanine and its derivatives into the biosynthetic
pathways of A. terreus was investigated to enhance the production of modified aromatic
metabolites. The study examined six phenylalanine derivatives: phenylalanine,
dihydroxyphenylalanine, β-phenylalanine, fluoro-phenylalanine, chloro-phenylalanine, and
bromo-phenylalanine. Each derivative was isolated and purified through similar extraction
protocols, ensuring consistency and comparability in the resulting fractions. The fractions were
then subjected to Minimum Inhibitory Concentration (MIC) assays to evaluate their
antimicrobial efficacy against Staphylococcus aureus and Escherichia coli. Further chemical
analysis was conducted using solid-phase extraction (SPE) and high-performance liquid
chromatography (HPLC) to separate and identify the compounds present.
This study demonstrates the potential of A. terreus in generating bioactive secondary
metabolites through PDB, offering a promising strategy for the development of novel
antimicrobial agents. The findings highlight the importance of investigating fungal metabolites
and metabolic engineering to enhance the biosynthetic capacity of microorganisms, in
response to the demand of new antibiotics due to rising antimicrobial resistance. |
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