Production of scopularide A in submerged culture with Scopulariopsis brevicaulis.

Background: Marine organisms produce many novel compounds with useful biological activity, but are currently underexploited. Considerable research has been invested in the study of compounds from marine bacteria, and several groups have now recognised that marine fungi also produce an interesting range of compounds. During product discovery, these compounds are often produced only in non-agitated culture conditions, which are unfortunately not well suited for scaling up. A marine isolate of Scopulariopsis brevicaulis, strain LF580, produces the cyclodepsipeptide scopularide A, which has previously only been produced in non-agitated cultivation.

Results: Scopulariopsis brevicaulis LF580 produced scopularide A when grown in batch and fed-batch submerged cultures. Scopularide A was extracted primarily from the biomass, with approximately 7% being extractable from the culture supernatant. By increasing the biomass density of the cultivations, we were able to increase the volumetric production of the cultures, but it was important to avoid nitrogen limitation. Specific production also increased with increasing biomass density, leading to improvements in volumetric production up to 29-fold, compared with previous, non-agitated cultivations. Cell densities up to 36 g L-1 were achieved in 1 to 10 L bioreactors. Production of scopularide A was optimised in complex medium, but was also possible in a completely defined medium.

Conclusions: Scopularide A production has been transferred from a non-agitated to a stirred tank bioreactor environment with an approximately 6-fold increase in specific and 29-fold increase in volumetric production. Production of scopularide A in stirred tank bioreactors demonstrates that marine fungal compounds can be suitable for scalable production, even with the native production organism.