摘要
Streptomycetes possess numerous gene clusters and the potential to produce a large amount of natural products.Histone deacetylase(HDAC)inhibitors play an important role in the regulation of histone modifications in fungi,but their roles in prokaryotes remain poorly understood.Here,we investigated the global effects of the HDAC inhibitor,sodium butyrate(SB),on marine-derived Streptomyces olivaceus FXJ 8.021,particularly focusing on the activation of secondary metabolite biosynthesis.The antiSMASH analysis revealed 33 secondary metabolite biosynthetic gene clusters(BGCs)in strain FXJ 8.021,among which the silent lobophorin BGC was activated by SB.Transcriptomic data showed that the expression of genes involved in lobophorin biosynthesis(ge00097–ge00139)and CoA-ester formation(e.g.,ge02824),as well as the glycolysis/gluconeogenesis pathway(e.g.,ge01661),was significantly up-regulated in the presence of SB.Intracellular CoA-ester analysis confirmed that SB triggered the biosynthesis of CoA-ester,thereby increasing the precursor supply for lobophorin biosynthesis.Further acetylomic analysis revealed that the acetylation levels on 218 sites of 190 proteins were up-regulated and those on 411 sites of 310 proteins were down-regulated.These acetylated proteins were particularly enriched in transcriptional and translational machinery components(e.g.,elongation factor GE04399),and their correlations with the proteins involved in lobophorin biosynthesis were established by protein–protein interaction network analysis,suggesting that SB might function via a complex hierarchical.
基金
supported by the National Key R&D Program of China(Grant No.2020YFA0907800)
the National Natural Science Foundation of China(Grant Nos.32170043 and 82173720).
