Enhancement of Echinocandin B Production by a UV- and Microwave-Induced Mutant of Aspergillus nidulans with Precursor- and Biotin-Supplying Strategy.

Abstract

Echinocandin B belongs to lipopeptide antifungal antibiotic bearing five types of direct precursor amino acids including proline, ornithine, tyrosine, threonine, and leucine. The objective of this study is to screen over-producing mutant in order to improve echinocandin B production; a stable mutant Aspergillus nidulans ZJB12073, which can use fructose as optimal carbon source instead of expensive mannitol, was selected from thousand isolates after several cycles of UV and microwave irradiation in turn. The results showed that mutant strain ZJB12073 exhibited 1.9-fold improvement in echinocandin B production to 1656.3 ± 40.3mg/L when compared with the parent strain. Furthermore, the effects of precursor amino acids and some chemicals on echinocandin B biosynthesis in A. nidulans were investigated, respectively. Tyrosine, leucine, and biotin were selected as key factors to optimize the medium employing uniform design method. The results showed that the optimized fermentation medium provided another 63.1% increase to 2701.6 ± 31.7mg/L in final echinocandin B concentration compared to that of unoptimized medium.