PRODUCTION OF THE CYTOSTATIC AGENT AEROPLYSININ BY THE SPONGE VERONGIA-AEROPHOBA IN INVITRO CULTURE

1. The marine sponge Verongia aerophoba contains two bioactive secondary metabolites from tyrosine, (+)-aeroplysinin-I [3',5'-dibromo-1',2'-dihydroxy-4'-methoxycyclohexa-3',5'-dien-1'-yl-methylcyanide; abbreviated AP] and dibromoverongia-quinol [3',5'-dibromo-1'-hydroxy-4'-oxocyclohexa-2',5'-dien-l'-yl-acetamide; abbreviated DV], which display strong cytostatic activity. 2. The concentrations causing 50% inhibition of cell growth are 0.47-mu-M (AP) and 1.21-mu-M (DV), resp. 3. Depending on depth regions from which the sponges were collected, differences in occurrence of metabolites were observed. 4. AP and DV were found to be present in sponges collected at a depth of 5-1 0 m, whereas only DV could be detected in material from deeper regions (20-30 m). 5. AP is present only in the surface layers (both the outer and oscular region) of the sponge, while in the centre of the sponge only DV is detected. 6. Cubes from sponges, collected at a depth of 30 m, were cultivated in seawater in vitro and were found to have the capacity (i) to synthesize AP, and (ii) to release this bioactive material into the medium under defined conditions. Under optimal conditions (light and aeration) 100 g of sponge synthesize and release 13.02 mg of AP during a 10-day incubation period. 7. In the dark and without aeration this synthesis was prevented. 8. These data show that also under in vitro conditions sponges retain the capability of producing bioactive compounds and can be induced to produce even substances which they did not secrete in their natural environment.