Biosynthesis of indocarbazostatin B, incorporation of D-[U-13C] glucose and L-[2-13C] tryptophan.
High incorporation of D-[U-13C] glucose and L-[indole-2-13C] tryptophan into indocarbazostatin B (2) was observed in a biosynthetic study using a mutant strain, Streptomyces sp. MUV-7-8. The original strain, Streptomyces sp. TA-0403 produced a small amount of indocarbazostatin (1) and indocarbazostatin B (2), which displayed potent biological activities. To facilitate biosynthetic studies, we selected high indocarbazostatin producing mutant strains. The first mutants, Streptomyces sp. MUV-6-83 and MUV-6-17, produced indocarbazostatins C (3) and D (4) as well as 1 and 2. When the production medium was supplemented with D-tryptophan, the MUV-6-17 mutant produced K252c (5), whereas when L-tryptophan was added, it produced K252d (6). On further UV treatment of the mutant strain MUV-6-83, we finally obtained a new mutant producer, Streptomyces sp. MUV-7-8, that produced 2 as a major metabolite with higher productivity. This mutant producer enabled us to do a feeding experiment of the envisioned precursors, glucose and tryptophan.
Feng
Yufei
Y
Graduate School of Agriculture, Hokkaido University, North-9, West-9, Kita-ku, Sapporo 060-8589, Japan.
Mitsuhashi
Shinya
S
Kishimoto
Takao
T
Ubukata
Makoto
M
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism*; D005285:Fermentation; D005947:Glucose / Q000378:metabolism*; D026121:Indole Alkaloids; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009154:Mutation / Q000502:physiology; D013056:Spectrophotometry, Ultraviolet; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002227:Carbazoles; D026121:Indole Alkaloids; D007211:Indoles; C458887:indocarbazostatin B; D014364:Tryptophan; C049985:staurosporine aglycone; D005947:Glucose