Chapter 11 : Regulation of Antibiotic Biosynthesis in Producer Organisms

Abstract:

Of the circa 12,000 known antibiotics, it has been estimated that some 160 are or have been in human clinical use. Streptomycetes, gram-positive filamentous bacteria, account for these production of about 55% of the commercially significant antibiotics. The Abs knockout leads to precocious production of all the Streptomyces coelicolor antibiotics in hours to days and in amounts up to 60-fold higher than normal, dependent on the culture conditions. The most extensive analysis of regulation of a specific antibiotic pathway, one step down from the Abs global regulators, is probably in Streptomyces virginiae in production of the two antibiotics virginiamycin M1 and virginiamycin S1. The hydrophobic side chain of the butyrolactones, known generically also as butaneolides, is in the same locus as the N-acyl moiety of the gram-negative quorum molecules. A schematic for regulation of biosynthetic gene expression for the major classes of streptomycete antibiotics (polyketides, nonribosomal peptides, and aminoglycosides) is beginning to take shape. Plant pathogenic bacteria often secrete enzymes (exoenzymes) with hydrolytic capacity to destroy the components of plant cell walls to release the nutrients that can then be utilized by the pathogens. The N-acylhomoserine lactones of Erwinia, Pseudomonas, and many other bacteria and the γ-butyrolactones of streptomycetes, serve equivalent purposes, as low-molecular-weight pheromones, for communicating population density-dependent signals between bacteria of the same species.