Biosynthesis of the macrolide antibiotic chlorothricin: basic building blocks.

Area of Science:

• Microbiology
• Biochemistry
• Natural Product Synthesis

Background:

• Chlorothricin is a macrolide antibiotic produced by Streptomyces antibioticus.
• Understanding the biosynthesis of antibiotics is crucial for developing new antimicrobial agents.

Purpose of the Study:

• To elucidate the biosynthetic pathway of chlorothricin.
• To identify the precursor molecules incorporated into the chlorothricin structure.

Main Methods:

• Feeding experiments using 14C- and 3H-labeled precursors.
• Analysis of precursor incorporation into the macrolide aglycone and specific moieties.

Main Results:

• Acetate and propionate are incorporated into the macrolide aglycone.
• Glucose contributes to the aglycone and is a specific precursor for the 2-deoxyrhamnose moiety.
• Tyrosine contributes carbons to the aglycone, while methionine provides an O-methyl group for the 6-methylsalicylic acid moiety.

Conclusions:

• The biosynthesis of chlorothricin involves the incorporation of acetate, propionate, glucose, and tyrosine.
• A unique pathway involving a hydrogen shift is proposed for the formation of the 2-deoxyrhamnose moiety.
• The 6-methylsalicylic acid component is derived from acetate and methionine.