Enhancement of Pneumocandin B0 Production in Glarea lozoyensis by Low-Temperature Adaptive Laboratory Evolution

Abstract

The production of pneumocandin B0 is limited by feedback inhibition. Here, low-temperature adaptive laboratory evolution (ALE) was used to improve the production capacity of Glarea lozoyensis by enhancing its membrane permeability. After 50 cycles of ALE, the pneumocandin B0 production of the endpoint strain (ALE50) reached 2131 g/L, which was 32% higher than the starting strain (ALE0). ALE50 showed a changed fatty acid composition of the cell membrane, which-+h increased its permeability by 14%, which in turn increased the secretion ratio threefold. Furthermore, ALE50 showed increased intracellular proline and acetyl-CoA concentrations, superoxide dismutase (SOD), and catalase (CAT) activity, as well as total antioxidant capacity. The slight biomass decrease in ALE50 was accompanied by decreased isocitrate dehydrogenase (ICDH) and glucose-6-phosphate dehydrogenase (G6PDH) activity. Finally, a putative model of the accumulation and secretion of pneumocandin B0 in ALE50 was established. ALE is a promising method to release intracellular feedback inhibition.

Alterations in the Gut Fungal Community in a Mouse Model of Huntington’s Disease

“…On the other hand, Glarea lozoyensis was more prevalent in healthy controls. G. lozoyensis is a natural producer of the antimicrobial compound pneumocandin B0, which is capable of inhibiting the growth of fungal pathobionts like C. albicans ( 68 , 69 ). Furthermore, Malassezia restricta and Yarrowia lipolytica were underrepresented in the HD gut mycobiome at 12 weeks of age.…”

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

“…Wild-type strains of G. lozoyensis predominantly synthesize pneumocandin A 0 , approximately 10 times more than pneumocandin B 0 [240]. As a result of CSI programs, HY producers of pneumocandin B 0 were obtained, which in its structure is less similar to echinocandin B than pneumocandin A 0 [180,[249][250][251]. Now, industrial strains produce hundreds of times more pneumocandin B 0 compared to WT strains [180].…”

“…As a result of CSI programs, HY producers of pneumocandin B 0 were obtained, which in its structure is less similar to echinocandin B than pneumocandin A 0 [180,[249][250][251]. Now, industrial strains produce hundreds of times more pneumocandin B 0 compared to WT strains [180]. One of the most important antibiotics of this class, semisynthetic micafungin, is derived from the natural product FR901379 (via the enzymatic synthesis of compound FR179642) [252,253].…”