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

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 stu...

Full description

Saved in:
Bibliographic Details
Published in:Applied microbiology and biotechnology 2021-09, Vol.105 (18), p.6707-6718
Main Authors: Dong, Yan, Zhang, Lei, Zhang, Weiting, Cao, Jianan, Wei, Yiping, Song, Ping, Xu, Qing
Format: Article
Language:English
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0175-7598
1432-0614
DOI:10.1007/s00253-021-11522-5