Candicidin biosynthesis in Streptomyces griseus

Area of Science:

• Microbial biosynthesis of complex natural products.
• Molecular genetics and genomics of antibiotic production.
• Biochemistry of polyketide synthases (PKS).

Background:

• Candicidin is an aromatic polyene macrolide antibiotic produced by Streptomyces griseus.
• Its biosynthesis involves p-aminobenzoic acid (PABA), acetate, and propionate units, with mycosamine attachment.
• Understanding candicidin biosynthesis is crucial for developing new antimicrobial agents.

Purpose of the Study:

• To identify and characterize genes involved in candicidin biosynthesis.
• To elucidate the regulatory mechanisms controlling candicidin production.
• To explore the potential for creating novel polyene antibiotics.

Main Methods:

• Isolation and partial sequencing of a 205-kb DNA region from Streptomyces griseus.
• Use of a p-aminobenzoic acid (PABA) synthase gene probe (pabAB).
• Analysis of gene expression via mRNA detection and study of phosphate regulation.

Main Results:

• Identification of genes encoding polyketide synthase (PKS), thioesterase, deoxysugar biosynthesis, modification, transport, and regulatory proteins.
• Demonstration that phosphate significantly represses the expression of candicidin biosynthesis genes.
• Detection of specific mRNAs only in the production medium, not in phosphate-supplemented or inoculum media.

Conclusions:

• The modular architecture of the candicidin PKS provides a basis for combinatorial biosynthesis.
• Insights into phosphate regulation offer targets for optimizing antibiotic yield.
• Potential exists for engineering novel, improved polyene antibiotics through genetic manipulation.