Production of actinorhodin-related "blue pigments" by Streptomyces coelicolor A3(2)

The genetically well-known strain Streptomyces coelicolor A3(2) produces the pH indicator (red/blue) antibiotic actinorhodin, but not all the "blue pigment" produced by this strain is actinorhodin. When the organism was subjected to various nutrient limitations (ammonium, nitrate, phosphate, or trace elements), and also during growth cessation caused by a relatively low medium pH, blue pigment production was initiated but the pigment and its location varied. At pH 4.5 to 5.5, significant formation of actinorhodin occurred and was located exclusively intracellularly. At pH 6.0 to 7.5 a different blue pigment was produced intracellularly as well as extracellularly. It was purified and identified as gamma-actinorhodin (the lactone form of actinorhodin). Analysis of act mutants of S. coelicolor A3(2) confirmed that both pigments are derived from the act biosynthetic pathway. Mutants with lesions in actII-ORF2, actII-ORF3, or actVA-ORF1, previously implicated or suggested to be involved in actinorhodin export, were impaired in production of gamma-actinorhodin, suggesting that synthesis of gamma-actinorhodin from actinorhodin is coupled to its export from the cell. However, effects on the level of actinorhodin production were also found in some mutants.

[1]  D. Hopwood.  Genetic manipulation of Streptomyces : a laboratory manual , 1985 .

[2]  W. Champness,et al.  Mutations in a new Streptomyces coelicolor locus which globally block antibiotic biosynthesis but not sporulation , 1990, Journal of bacteriology.

[3]  D. Hopwood,et al.  Actinorhodin is a chromosomally-determined antibiotic in Streptomyces coelicolar A3(2). , 1976, Journal of general microbiology.

[4]  D. Erikson.  Loss of aerial mycelium and other changes in Streptomycete development due to physical variations of cultural conditions. , 1955, Journal of general microbiology.

[5]  B. Rudd,et al.  Identification of a red pigment from Streptomyces coelicolor A3(2) as a mixture of prodigiosin derivatives. , 1985, The Journal of antibiotics.

[6]  S. Horinouchi,et al.  Production in Large Quantities of Actinorhodin and Undecylprodigiosin Induced by afsB in Streptomyces lividans , 1984 .

[7]  M. Bibb,et al.  Stationary‐phase production of the antibiotic actinorhodin in Streptomyces coelicolor A3(2) is transcriptionally regulated , 1993, Molecular microbiology.

[8]  S. Ōmura,et al.  Letter: Nanaomycins A and B, new antibiotics produced by a strain of Streptomyces. , 1974, The Journal of antibiotics.

[9]  J. Caballero,et al.  DNA sequence and functions of the actVI region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor A3(2). , 1994, The Journal of biological chemistry.

[10]  C. Khosla,et al.  Engineered Biosynthesis of Novel Polyketides: actVII and actIV Genes Encode Aromatase and Cyclase Enzymes, Respectively , 1994 .

[11]  S. Hallam,et al.  Nucleotide sequence, transcription and deduced function of a gene involved in polyketide antibiotic synthesis in Streptomyces coelicolor. , 1988, Gene.

[12]  C. Edwards,et al.  Effects of Metals on Streptomyces coelicolor Growth and Actinorhodin Production , 1990, Applied and environmental microbiology.

[13]  S. Harding,et al.  Identification of a Flavin:NADH Oxidoreductase Involved in the Biosynthesis of Actinorhodin , 1995, The Journal of Biological Chemistry.

[14]  B. Rudd,et al.  Biosynthesis of the antibiotic actinorhodin. Analysis of blocked mutants of Streptomyces coelicolor. , 1987, The Journal of antibiotics.

[15]  A. Zeeck,et al.  Neue Isochromanchinon‐Antibiotica der Naphthocyclinon‐Reihe , 1983 .

[16]  Brian A. M. Rudd,et al.  Biosynthesis of actinorhodin. Determination of the point of dimerization , 1981 .

[17]  D. Hopwood,et al.  Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host , 1984, Nature.

[18]  H. Baylis,et al.  The stringent response in Streptomyces coelicolor A3(2) , 1991, Molecular microbiology.

[19]  H. V. Veen,et al.  Regulation of polyphosphate metabolism in Acinetobacter strain 210A grown in carbon- and phosphate-limited continuous cultures , 1992, Archives of Microbiology.

[20]  D. Hopwood,et al.  Physical and genetic characterisation of the gene cluster for the antibiotic actinorhodin in Streptomyces coelicolor A3(2). , 1986, Molecular & general genetics : MGG.

[21]  Y. Tashima,et al.  Control of rabbit liver fructose-1, 6-diphosphatase activity by magnesium ions. , 1975, Journal of biochemistry.

[22]  B. Rudd,et al.  Genetics of actinorhodin biosynthesis by Streptomyces coelicolor A3(2). , 1979, Journal of general microbiology.

[23]  A. Torriani-Gorini.  Phosphate metabolism and cellular regulation in microorganisms , 1987 .

[24]  W. C. Krueger,et al.  Kalafungin. II. Chemical transformations and the absolute configuration. , 1976, The Journal of antibiotics.

[25]  D. Hopwood,et al.  Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A3(2) including the polyketide synthase for the antibiotic actinorhodin. , 1992, The Journal of biological chemistry.

[26]  J. Caballero,et al.  The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of streptomyces , 1991, Cell.

[27]  Stephen G. Oliver,et al.  Pigmented antibiotic production by Streptomyces coelicolor A3(2): kinetics and the influence of nutrients , 1990 .

[28]  C. Khosla,et al.  Targeted gene replacements in a Streptomyces polyketide synthase gene cluster: role for the acyl carrier protein , 1992, Molecular microbiology.

[29]  H. Brockmann,et al.  Über Actinomycetenfarbstoffe, V. Mitteil.1): Zur Konstitution des Actinorhodins, III. Mitteil1) , 1955 .

[30]  W. Champness,et al.  Genetic analysis of absB, a Streptomyces coelicolor locus involved in global antibiotic regulation , 1992, Journal of bacteriology.