Abstract
Streptomycetes are an important source of natural products potentially applicable in the pharmaceutical industry. Many of these drugs are secondary metabolites whose biosynthetic genes are very often poorly expressed under laboratory cultivation conditions. In many cases, antibiotic-resistant mutants exhibit increased production of natural drugs, which facilitates the identification and isolation of new substances. In this study, we report the induction of a type II polyketide synthase gene cluster in the marine strain Streptomyces albus subsp. chlorinus through the selection of streptomycin-resistant mutants, resulting in overproduction of the novel compound fredericamycin C2 (1). Fredericamycin C2 (1) is structurally related to the potent antitumor drug lead fredericamycin A.
Highlights
The bacterial genus Streptomyces is well-known for producing a huge variety of bioactive secondary metabolites with potential pharmaceutical applications [1,2]
The strain S. albus subsp. chlorinus NRRL B-24108 was cultured in mannitol agar (MS agar) medium containing increasing concentrations of streptomycin
We present the novel variant fredericamycin C2 (1), which is overproduced by the strain S. albus subsp. chlorinus JR1, a spontaneous streptomycin-resistant mutant derived from S. albus subsp. chlorinus NRRL B-24108
Summary
The bacterial genus Streptomyces is well-known for producing a huge variety of bioactive secondary metabolites with potential pharmaceutical applications [1,2]. This approach is based on the work of Ochi and his team They discovered that certain mutations in the rpsL and rpoB genes, which code for the ribosomal protein S12 and the β-subunit of RNA polymerase, respectively, lead to an altered gene product that confers resistance to streptomycin (str mutants) or to rifampicin (rif mutants), respectively. The mutations in these genes increase the production of secondary metabolites in several Streptomyces strains [3,4,5,6,7]. The stringent response is triggered in E. coli [8] and other prokaryotic microorganisms [9,10]
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