Reevaluation of the violacein biosynthetic pathway and its relationship to indolocarbazole biosynthesis.
The biosynthetic pathways for violacein and for indolocarbazoles (rebeccamycin, staurosporine) include a decarboxylative fusion of two tryptophan units. However, in the case of violacein, one of the tryptophans experiences an unusual 1-->2 shift of the indole ring. The violacein biosynthetic gene cluster was previously reported to consist of four genes, vioABCD. Here we studied the violacein pathway through expression of vio genes in Escherichia coli and Streptomyces albus. A pair of genes (vioAB), responsible for the earliest steps in violacein biosynthesis, was functionally equivalent to the homologous pair in the indolocarbazole pathway (rebOD), directing the formation of chromopyrrolic acid. However, chromopyrrolic acid appeared to be a shunt product, not a violacein intermediate. In addition to vioABCD, a fifth gene (vioE) was essential for violacein biosynthesis, specifically for production of the characteristic 1-->2 shift of the indole ring. We also report new findings on the roles played by the VioC and VioD oxygenases, and on the origin of violacein derivatives of the chromoviridans type.
Sánchez
César
C
Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006 Oviedo, Spain.
Braña
Alfredo F
AF
Méndez
Carmen
C
Salas
José A
JA
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002861:Chromobacterium / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D015394:Molecular Structure; D019159:Nonheme Iron Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010105:Oxygenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D002227:Carbazoles; D007211:Indoles; D019159:Nonheme Iron Proteins; C053339:rebeccamycin; D010105:Oxygenases; C497198:vioC protein, Chromobacterium violaceum; C063155:violacein