Application of heavy-ion irradiation mutagenesis to improve the production efficiency of the antifungal drug micafungin

Heavy-ion irradiation, as a novel breeding method, has demonstrated high efficiency in creating diverse new mutants. Compared to other physical mutagenic sources, such as X-rays and γ-rays, disparities in both physical and biological effects are readily apparent. This method possesses distinct advantages, including strong penetration, extensive sample processing capabilities, and a wide range of mutagenic effects, thereby establishing itself as a highly potent and efficient mutagenic technique. In this study, FR901379 high producing strains were obtained through two rounds of heavy-ion irradiation, with a maximum titer of 1.1 g/L, which was enhanced by 253.7% over the parent strain. The high-yield mutants displayed obvious differences in morphology and fermentation compared to the parent strain, and regular mycelium pellet and lower viscosity of the fermentation broth were beneficial for the synthesis of FR901379.

In addition, to evaluate the impact of nonhomologous end-joining deficient strain as irradiated materials on the diversity of mutagenesis libraries, mutants were selected from the irradiated MEFC09-Δku80 mutant library. The results showed that end-joining deficient strain is more sensitive to heavy-ion radiation, resulting in higher lethality rates at the same radiation dose, as well as more InDels, SNPs, SVs, and MDS mutations. The use of end-joining deficient strain as irradiated materials increases the diversity of the mutagenesis library.

Further comparative genomic analysis demonstrated that heavy-ion irradiation mutagenesis presumably altered the genes of multiple key enzymes in morphological differentiation while enhancing the FR901379 synthesis in the high-yield mutants. The transcriptome results suggested that the increase in FR901379 production should be attributed to the upregulation of mcfA.

See the article: Improving the production of micafungin precursor FR901379 in Coleophoma empetri using heavy-ion irradiation and its mechanism analysis