Directed biosynthesis of new indolmycins

Area of Science:

• Microbiology
• Biotechnology
• Medicinal Chemistry

Background:

• Indolmycin is an antibiotic with lipophilic properties.
• Modifying antibiotic structures can alter their activity and properties.

Purpose of the Study:

• To investigate the effect of tryptophan concentration on indolmycin production.
• To explore directed biosynthesis for creating more hydrophilic indolmycin derivatives.
• To assess the antimicrobial activity of modified indolmycin.

Main Methods:

• Culturing Streptomyces griseus ATCC 12648 with varying tryptophan concentrations.
• Introducing modified tryptophan and indole precursors to alter the antibiotic's aromatic ring.
• Analyzing derivatives using thin-layer chromatography and mass spectrometry.

Main Results:

• A tryptophan concentration of 0.4 microgram/ml increased indolmycin production by 37%.
• Substitution with methoxy or hydroxy groups in the 5-position reduced lipophilicity.
• Hydrophilic derivatives showed slightly enhanced antimicrobial activity without altering the Gram-positive/Gram-negative activity ratio.
• Substitutions in the 6-position were not incorporated, and all modified precursors reduced antibiotic titer.

Conclusions:

• Directed biosynthesis can modify indolmycin's lipophilicity.
• Specific precursor modifications can enhance antimicrobial activity moderately.
• Precursor substitution position significantly impacts incorporation and antibiotic yield.