Biosynthesis of Kitasamycin(Leucomycin) by Leucine Analog-Resistant Mutants of Streptomyces kitasatoensis
AUTOR(ES)
Vézina, Claude
RESUMO
The biosynthesis of kitasamycin in Streptomyces kitasatoensis B-896 was profoundly influenced by the addition of precursors to complex and defined media: l-valine and l-leucine directed biosynthesis towards the pairs A4/A5 (R2 = butyryl) and A1/A3 (R2 = isovaleryl), respectively, and total kitasamycin titers were doubled and quadrupled, respectively. S. kitasatoensis B-896 was very resistant (>20 mg/ml) to α-aminobutyric acid, an analog of l-valine, but very susceptible to l-leucine analogs 5′, 5′, 5′-trifluoroleucine and 4-azaleucine (5 to 10 μg/ml). The inhibition by 4-azaleucine could be reversed by l-leucine, but by none of the other amino acids of the pyruvate family or the amino acids of the aspartate pathway. 4-Azaleucine-resistant mutants were isolated which in the absence of any precursors overproduced l-leucine and a kitasamycin complex mainly consisting of the pair A1/A3. These 4-azaleucine-resistant mutants are presumed to be regulatory mutants in which α-isopropylmalate synthase, the first enzyme of the l-leucine pathway, has become either derepressed or desensitized to leucine feedback inhibition. l-Leucine-regulatory mutants have economic value: in the absence of expensive precursors, they produce a kitasamycin complex in which the most potent pair A1/A3 is dominant and the least active components are absent.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=352747Documentos Relacionados
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