Aims: This work aimed to improve the production of anti-tubercular hirsutellones by the insect pathogenic fungus Hirsutella nivea BCC 2594.
Methods and results: The fungus was cultivated under different carbon/nitrogen sources and aerations (shake vs static flasks) to improve the production of the anti-tubercular alkaloids, hirsutellones A-D. Under the basal conditions, static cultivation at 25 degrees C in minimum salt medium, only hirsutellone B and C were detected with maximum concentrations of 139.00 and 18.27 mg l(-1). Substitution of fructose for glucose and peptone for yeast extract increased the titres of hirsutellones A, B and C about two- to threefold. However, hirsutellone D was not detected in this medium. Culture agitation induced the production of hirsutellone D. As a result, the significant amounts of hirsutellones A-D were obtained with the concentration of 29.93, 169.63, 22.65 and 15.71 mg l(-1) within 15 days.
Conclusions: Improved titres of hirsutellones in H. nivea BCC 2549 were achieved with an agitated (200 rev min(-1)) fructose-peptone medium at 25 degrees C.
Significance and impact of the study: Improved yields of hirsutellones B-D will enable medicinal chemistry modifications leading to a development of a potential candidate for tuberculosis therapy.