Screening and production of arylsulfatases for target therapy with etoposide 4'-sulfate, an antitumor prodrug.
Two arylsulfatase-producing streptomycetes that desulfated etoposide 4'-sulfate were isolated from soil samples. Taxonomical study identified one soil isolate as Streptomyces griseorubiginosus S980-14 (Es-1 arylsulfatase producer), while the other was considered new and tentatively designated Streptomyces sp. T109-3 (Es-2 arylsulfatase producer). Both strains produced extracellular arylsulfatase activities, provided that cultivation media were prepared with distilled water. Unlike the two known types of arylsulfatases, which had significant activity on p-nitrophenyl sulfate but none on etoposide 4'-sulfate, the crude streptomycete arylsulfatases efficiently desulfated etoposide 4'-sulfate and p-nitrophenyl sulfate, which supports the establishment of a new type of arylsulfatases.
Yamamoto
S
S
Bristol-Myers Squibb Research Institute, Tokyo, Japan.
Ueki
T
T
Tomita
K
K
Ohnuma
T
T
Sawada
Y
Y
Fukagawa
Y
Y
Oki
T
T
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001192:Arylsulfatases / Q000096:biosynthesis*; D002240:Carbohydrate Sequence; D005047:Etoposide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005285:Fermentation; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D013302:Streptomyces / Q000145:classification / Q000201:enzymology* / Q000648:ultrastructure; D013463:Sulfuric Acid Esters / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011355:Prodrugs; D013463:Sulfuric Acid Esters; C094687:etoposide 4'-sulfate; D005047:Etoposide; D001192:Arylsulfatases