Genetics and biochemistry on tylosin production: a model for genetic engineering in antibiotic-producing Streptomyces.

Abstract

Antibiotics are economically-important chemicals produced by a variety of species of prokaryotic and eukaryotic microorganisms. Species of the prokaryotic genus, Streptomyces, produce about 70 percent of all known antibiotics (19). Therefore, the Streptomyces present a practical model for genetic manipulation. Streptomyces are also fundamentally interesting for at least two reasons. First, they undergo a differentiation cycle of spore germination, mycelial growth, aerial mycelium formation and sporulation (17). In general, the relationships between the differentiation cycles and antibiotic production are only poorly understood. Second, the Streptomyces contain circular genomes (17,19) with guanine plus cytosin (G+C) contents of 69 to 73 percent (49). This G+C content approaches the genetic code upper limit (50), beyond which the amino acid content of proteins would have to deviate substantially from the bacterial norm. Since the latter is highly unlikely (47), the Streptomyces must have severely constrained codon usage patterns which should maximize the G+C content in the third position of codons. It is not known if there are additional constraints in noncoding sequences which, for instance, might affect promoter sequences.