Skip to content

Integrated proteomic and acetylomic analyses reveal the metabolic reprogramming associated with increased tylosin-equivalent concentration in Streptomyces xinghaiensis sf106-B1.

Aug 2026 · Microbiology Research · Vol 313, pp. 128669 · 0 citations · 72 references
Medicine

Abstract

Deciphering the metabolic basis of high-yield antibiotic production in Streptomyces is crucial for strain optimization. Atmospheric and room-temperature plasma (ARTP) mutagenesis of Streptomyces xinghaiensis sf106 generated a mutant with a 30% increase in tylosin-equivalent concentration (μg/mL). 4D-FastDIA quantitative proteomics identified 279 differentially abundant proteins enriched in the Type I polyketide synthase (PKS) pathway, with increased abundance of key macrolide-biosynthesis-related proteins. Lysine-acetylome profiling identified 1152 differentially abundant acetylation sites and revealed altered acetylation of enzymes involved in fatty acid metabolism and the tricarboxylic acid (TCA) cycle, suggesting adjustments in central metabolism associated with acyl-CoA precursor availability and energy generation. Integration of proteomic and acetylomic data suggests coordinated changes in protein abundance and lysine acetylation associated with the increased tylosin-equivalent concentration. These results highlight candidate nodes for rational metabolic engineering of S. xinghaiensis.

View source

Similar papers

Jul 2026

Proteomic Insights into Salt-Stress Tolerance in Zygosaccharomyces rouxii Revealed by Data-Independent Acquisition Mass Spectrometry.

Under severe stress, GO and KEGG enrichment consistently revealed the reinforcement of central carbon and energy metabolism, peroxisome-associated fatty acid turnover, oxidoreductase/redox activities, and translation and nucleotide metabolic pathways.

Dingkang Wang, Li Wang, Yue Xiao et al. · 0 citations
Open access Aug 2026

Acidic Stress Induces Proteomic Reprogramming and Virulence-Associated Adaptation in Paracoccidioides brasiliensis

Paracoccidioidomycosis (PCM) is a neglected systemic mycosis whose etiologic agents must adapt to acidic host niches such as phagolysosomes. Here, we used quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics to define the response of Paracoccidioides brasiliensis to acidic stress (pH 4.5) versus control pH (6.5) after 5 and 24 h. We identified and quantified 4374 proteins, including 327 and 722 differentially abundant proteins at 5 and 24 h, respectively, revealing time-dependent proteomic reprogramming. Enrichment analyses highlighted proteolysis, protein metabolism, organonitrogen metabolism, MAPK- and SNF1-like signaling, central carbon metabolism, tyrosine metabolism, and ergosterol biosynthesis as major acid-responsive processes. Complementary assays showed pH-dependent extracellular proteolytic activity, increased adhesion to A549 pulmonary epithelial cells, and dynamic ergosterol remodeling. The proteomic data further indicated increased abundance of moonlighting proteins linked to adhesion and metabolic enzymes associated with ATP generation and melanin precursor production. Together, these findings indicate that P. brasiliensis adapts to acidic environments through coordinated regulation of proteostasis, metabolism, signaling, host-cell interaction, and membrane homeostasis, supporting survival and virulence potential in acidic host microenvironments.

Reinaldo Souza Oliveira, Maria Cecilia Gordijo, W. Segura et al. · 0 citations
Open access Jul 2026

Comparative proteomics and metabolomics reveals distinct host protein quality control and metabolic signatures during recombinant IL1-His and IL15-His expression in Nicotiana benthamiana

Findings underscore that the characteristics of the target protein and its interaction with the host's physiology could influence the yield of the recombinant protein production in plants.

A. Savinova, Theerakarn Srisangsung, Pipob Suwanchaikasem et al. · 0 citations
Aug 2026

Integrated physiology, transcriptomics and targeted metabolomics reveal a potential quorum sensing network involved in the initial spore density-dependent regulation of morphogenesis and polyketide biosynthesis in Monascus.

Density dependence is a key characteristic of quorum sensing (QS) in fungi; however, no relevant reports have been found in Monascus. Therefore, this study aimed to investigate the effects of initial spore density on the morphological development and polyketide secondary metabolism of Monascus purpureus to elucidate the regulatory role of QS. At the high initial spore density, more active conidial development and secondary metabolism were observed in the early fermentation stage, accompanied by rougher hyphal surfaces, increased secretion and larger vacuoles. Gene set enrichment analysis (GSEA) based on transcriptomic data revealed that high initial spore density activated ribosome biosynthesis to support rapid cell growth and secondary metabolism, whereas low initial spore density upregulated genes associated with peroxisome biosynthesis, the enzymatic antioxidant system, fatty acid degradation, fatty acid biosynthesis, and asexual sporulation. Furthermore, the reduction in linoleic acid content at high initial spore density suggested that linoleic acid and its derivatives may function as putative quorum sensing molecules (QSMs). Finally, a potential regulatory network integrating initial spore density with secondary metabolism and development was proposed. These findings enhance the understanding of the QS network in Monascus and offer a theoretical basis for the optimization of fermentation processes.

Jiaxing Li, Huijing Zhang, Xizi Zhang et al. · 0 citations
Open access Jul 2026

Snapshot at Saccharomycopsis fibuligera metabolism for industrial terpenoid production and bioengineering.

BACKGROUND Microbial metabolic engineering increasingly depends on identifying robust non-conventional yeast chassis with favorable metabolic traits. Although Saccharomyces cerevisiae remains the main model for isoprenoid engineering, alternative yeasts may provide superior native precursor availability. Here, we report the first comparative metabolomic characterization of Saccharomycopsis fibuligera, focusing on the mevalonate and terpenoid backbone biosynthesis pathways. RESULTS LC-MS profiling revealed elevated levels of acetyl-CoA, HMG-CoA, and MVA in S. fibuligera, suggesting strong native flux through the MVA pathway. The universal isoprenoid precursors IPP and DMAPP accumulated at substantially higher levels than in S. cerevisiae, together with enrichment of FPP and ergosterol abundance, indicating efficient channeling toward sterol biosynthesis. Conversely, upper glycolysis metabolites were reduced, while TCA cycle intermediates were enriched, supporting the proposed Crabtree-negative phenotype of S. fibuligera. Amino acid profiling also indicated enhanced nitrogen storage capacity. CONCLUSIONS These results position S. fibuligera as a metabolically favorable platform with high intrinsic MVA pathway activity and precursor availability for terpenoid production, highlighting its strong potential as an emerging microbial chassis for next‑generation terpenoid bioproduction.

Alejandro Lopez-Barbera, H. Torrell, Nerea Abasolo et al. · 0 citations