Comparative Transcriptome Analysis of Streptomyces nodosus Mutant With a High-Yield Amphotericin B

Abstract

Antibiotics play an important role in human health. Most antibiotics are derived from microbial secondary metabolites. Amphotericin is a polyene macrolide antibiotic synthesized by Streptomyces nodosus. S. nodosus ZJB2016050 with high-yield amphotericin B (AmB) was obtained by traditional mutagenesis using S. nodosus ATCC14899 as the original strain. The differences in the characterization of the two strains were found in color, mycelium morphology, and AmB yield. Subsequent comparative transcriptome explained the yield differences between the two strains. Pathways including the carbohydrate metabolic pathway and the secondary product synthesis pathway were targeted. The upregulation of glucokinase, phosphoglycerate mutase, and pyruvate dehydrogenase accelerates the consumption of glucose and has great effects on the accumulation of precursors. One of the competitive secondary metabolites of the polyketone synthetase (PKS) II type sapromomycin analog synthesis gene cluster was downregulated, which competes for malonyl-CoA. Five PKS modules (except for the first module amphA) of the amphotericin synthetic gene cluster in the high-yielding strain were downregulated, which resulted in the total amphotericin A (AmA) and AmB of S. nodosus ZJB2016050 being less than that of the wild-type S. nodosus ATCC14899. Combined with gene differential expression in the pentose phosphate pathway and the reaction mechanism of the ER5 domain, the reason that S. nodosus ZJB2016050 preferred to synthesize AmB was probably related to intracellular reduction.

Enhancing the production of amphotericin B by Strepyomyces nodosus in a 50-ton bioreactor based on comparative genomic analysis

“…In previous research, the expression levels of some key genes in the glycolysis and precursor metabolism pathways of S. nodosus ZJB2016050 were higher than those of the wild-type S. nodosus ATCC14899 (Huang et al 2021). The accumulation of AmB was the fastest from 24 to 48 h. At 96 h, the yields of S. nodosus ZJB2016050 and S. nodosus ATCC14899 were 9.73 mg/g and 7.5 mg/g, respectively (Fig.…”

The Antifungal Mechanism of Isoxanthohumol from Humulus lupulus Linn.

“…Carbohydrates are the main carbon sources in the TCA cycle, and inhibition of them would cause damage to the metabolic pathways. Carbohydrate metabolism is one of the main metabolic pathways and forms of energy supply in fungi, including biochemical pathways for biosynthesis, degradation, interconversion, and energy metabolism [ 20 , 21 ]. Effect of isoxanthohumol on the mycelial metabolism was evaluated ( Figure 9 ).…”

Comparative proteomics analysis of adult Haemonchus contortus isolates from Ovis ammon

“…SHMT not only plays a significant role in carbon metabolism but also is involved in the biosynthesis of antibiotics, which could be extensively applied in the treatment of cancers and the development of antibiotics ( Wang et al., 2022 ). Comparative transcriptome analysis of Streptomyces nodosus mutants showed that upregulated pyruvate dehydrogenase can accelerate the consumption of glucose and has great effects on the accumulation of precursors, in which antibiotics are derived from microbial secondary metabolites ( Huang et al., 2021 ). A previous report showed that intermediary metabolism and respiration by DLD were affected by ethambutol and could be explored as additional drug targets ( Ghiraldi-Lopes et al., 2019 ).…”

“…From red to green (score 0-2), it means the Domain (P<0.05) -log10(Fisher's exact p value). of precursors, in which antibiotics are derived from microbial secondary metabolites (Huang et al, 2021). A previous report showed that intermediary metabolism and respiration by DLD were affected by ethambutol and could be explored as additional drug targets (Ghiraldi-Lopes et al, 2019).…”