Unique butyric acid incorporation patterns for salinosporamides A and B reveal distinct biosynthetic origins.
Feeding sodium butyrate (0.25-1 mg/ml) to cultures of Salinispora tropica NPS21184 enhanced the production of salinosporamide B (NPI-0047) by 319% while inhibiting the production of salinosporamide A (NPI-0052) by 26%. Liquid chromatography mass spectrometry analysis of the crude extract from the strain NPS21184 fed with 0.5 mg/ml sodium [U-(13)C(4)]butyrate indicated that butyrate was incorporated as a contiguous four-carbon unit into NPI-0047 but not into NPI-0052. Nuclear magnetic resonance analysis of NPI-0047 and NPI-0052 purified from the sodium [U-(13)C(4)]butyrate-supplemented culture extract confirmed this incorporation pattern. The above finding is the first direct evidence to demonstrate that the biosynthesis of NPI-0047 is different from NPI-0052, and NPI-0047 is not a precursor of NPI-0052.
Tsueng
Ginger
G
Nereus Pharmaceuticals, 10480 Wateridge Circle, San Diego, CA 92121, USA.
McArthur
Katherine A
KA
Potts
Barbara C M
BC
Lam
Kin S
KS
D020148:Butyric Acid / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry* / Q000378:metabolism; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008848:Micromonosporaceae / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism
D007769:Lactams; D007783:Lactones; D011758:Pyrroles; D020148:Butyric Acid; C475865:marizomib; C504698:salinosporamide B