Glyap1 regulates pneumocandin B0 synthesis by controlling the intracellular redox balance in Glarea lozoyensis

• Published in: Applied microbiology and biotechnology Vol. 105; no. 18; pp. 6707 - 6718
• Main Authors: Dong, Yan, Zhang, Lei, Zhang, Weiting, Cao, Jianan, Wei, Yiping, Song, Ping, Xu, Qing
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2021; Springer Nature B.V
• Subjects: Antioxidants; Biomass; Biomedical and Life Sciences; Biosynthesis; Biotechnological Products and Process Engineering; Biotechnology; Carbon tetrachloride; Caspofungin; Catalase; Fungicides; Homology; Intracellular; Life cycles; Life Sciences; Metabolites; Microbial Genetics and Genomics; Microbiology; Oxidative stress; Phenotypes; Pneumocandin B0; Reactive oxygen species; Regulatory mechanisms (biology); Secondary metabolites; Sensitivity; Superoxide dismutase; Yeasts; Yes-associated protein; Oxidative stress; Pneumocandin B; Gl; ROS
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-021-11522-5

Pneumocandin B 0 , the precursor of the antifungal drug caspofungin, is a lipohexapeptide produced by the fungus Glarea lozoyensis . Oxidative stress and the resulting production of reactive oxygen species (ROS) are known to be involved in the regulation of pneumocandin B 0 biosynthesis. In this study, the Gl yap1 gene of Glarea lozoyensis , a homologue of the yeast redox regulator YAP1, was knocked out. The intracellular ROS levels of the resulting ΔGl yap1 strain were higher than in the wild-type strain, which was caused by the downregulated expression of superoxide dismutase (SOD) and catalase (CAT). Compared with the wild-type strain, ΔGl yap1 exhibited an oxidative phenotype throughout its life cycle, which resulted in significantly higher pneumocandin B 0 production per unit biomass. In addition, ΔGl yap1 showed growth inhibition and decreased pneumocandin B 0 production in the presence of CCl 4 , which leads to strong oxidative stress. To overcome the strain’s sensitivity, a three-stage antioxidant addition strategy was developed. This approach significantly improved the growth of ΔGl yap1 while maintaining a high pneumocandin B 0 production per unit biomass, which reached 38.78 mg/g DCW. Notably, this result represents a 50% increase over the wild-type strain. These findings provide new insights into the regulatory mechanisms that control pneumocandin B 0 production under oxidative stress, which may be applied to improve the production of other secondary metabolites. Key points • Glyap1 is involved in expression of redox and pneumocandin B 0 synthesis-related genes. • Addition of a three-stage antioxidant alleviated the sensitivity of ΔGlyap1 strain. • The yield of pneumocandin B 0 per unit biomass of ΔGlyap1 strain was 38.78 mg/g DCW.