Effects of trace elements on aspergiolide A biosynthesis by marine-derived filamentous fungus Aspergillus glaucus HB 1-19 were investigated. Cobalt (Co2+) and nickel (Ni2+) stimulated aspergiolide A biosynthesis while zinc (Zn2+) inhibited it. Equal cobalt (Co2+) addition at 48,72 and 96 h with total amount of 0.052 mM most effectively enhanced aspergiolide A production. The time courses indicated that mycelia growth, sugar utilization and aspergiolide A biosynthesis were enhanced by Co2+. Finally, feeding 0.052 mM Co2+ increased mycelia growth, sugar utilization and aspergiolide A production by 12.2%, 13.7% and 46.7%, respectively. The results of organic acids analysis indicated that extracellular pyruvate increased while fumarate decreased in Co2+ addition cultures. Moreover, feeding vitamin B-12, which combined cobalt to be a cofactor form, increased aspergiolide A production by 59.1%. This indicated Col functioned by facilitating pyruvate accumulation and increasing vitamin B-12 formation that were beneficial to aspergiolide A biosynthesis that is via polyketide pathway. (C) 2012 Elsevier Ltd. All rights reserved.