Precursor directed biosynthesis of aureobasidins.
The antifungal antibiotic aureobasidin A (AbA) is a cyclic depsipeptide composed of eight amino acids and a hydroxy acid. New Ab analogs were produced by feeding various amino acids to Aureobasidium pullulans R 106 c-712 in a chemically-defined medium containing glucose and ammonium sulfate. The constituent amino acids of AbA at positions 3 (L-phenylalanine), 4 (N-methyl-L-phenylalanine), 5 (L-proline), 6 (L-allo-isoleucine) and 8 (L-leucine) were replaced by respective analogous amino acids such as o-fluoro-L-phenylalanine, 4-hydroxy-L-proline, L-norleucine and L-norvaline, resulting in the production of eight new Ab analogs. This is the first paper to describe amino acid replacements at positions 3, 5 and 8. L-[1-13C]-Valine exogenously added was incorporated into the three valine-related moieties of AbA at positions 2, 7 (both N-methyl-L-valine) and 9 (beta-hydroxy-N-methyl-L-valine), but these moieties were never replaced by exogenous amino acid analogs. The comparative antifungal activities of AbA and the eight new Ab analogs were determined.
Takesako
K
K
Biotechnology Research Laboratories, Takara Shuzo Co., Ltd., Shiga, Japan.
Mizutani
S
S
Sakakibara
H
H
Endo
M
M
Yoshikawa
Y
Y
Masuda
T
T
Sono-Koyama
E
E
Kato
I
I
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000096:biosynthesis* / Q000737:chemistry* / Q000494:pharmacology; D047630:Depsipeptides; D008826:Microbial Sensitivity Tests; D003904:Mitosporic Fungi / Q000378:metabolism; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000378:metabolism; D013329:Structure-Activity Relationship; D014633:Valine / Q000378:metabolism
D000935:Antifungal Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C071398:aureobasidin A; D014633:Valine