Enhanced Production of Iturin A-2 Generated from Bacillus velezensis T701 and the Antitumor Activity of Iturin A-2 against Human Gastric Carcinoma Cells

Bacillus velezensis T701 was used to produce lipopeptide. Among the lipopeptide, iturin A-2 was of the highest antitumor activity. In order to get higher yield of iturin A-2, the fermentation conditions of strain T701 were modified by optimization of medium composition and culture conditions. It was found that the concentrations of sucrose and peptone, and fermentation time had a very significant effect on the yield of iturin A-2 and fermentation temperature had a great influence on both of the yield of iturin A-2 and the proportion of iturin A-2 in iturin A. Another important conclusion was that monovalent cation could enhance metabolic ability of strain T701 and promote the yield of iturin A-2. Finally, under the optimized fermentation conditions of strain T701, iturin A-2 accounted for 80.2% of iturin A in HPLC trace, compared with the reported value of 46.8%. The yield of iturin A-2 increased to 1056.9 mg l(-1). After separated and purified, pure iturin A-2 was achieved and confirmed by MS and NMR. The IC50 values of iturin A-2 against human gastric carcinoma cells NCI-N87 and MGC 803 were (51.7 +/- 5.7) and (41.2 +/- 4.3) mu g ml(-1), respectively. This is the first report on gram-scale preparation of iturin A-2 which also exhibits inhibitory activity against gastric cancer.