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Identification of transcriptional regulatory elements in the GC-rich Streptomyces genome is essential for the production of novel biochemicals from secondary metabolite biosynthetic gene clusters (smBGCs). Despite many efforts to understand the regulation of transcription initiation in smBGCs, information on the regulation of transcription termination and posttranscriptional processing remains scarce. In this study, we identified the transcriptional regulatory elements in β-lactam antibiotic-producing Streptomyces clavuligerus ATCC 27064 by determining a total of 1,427 transcript 3'-end positions (TEPs) using the term-seq method. Termination of transcription was governed by three classes of TEPs, of which each displayed unique sequence features. The data integration with transcription start sites and transcriptome data generated 1,648 transcription units (TUs) and 610 transcription unit clusters (TUCs). TU architecture showed that the transcript abundance in TU isoforms of a TUC was potentially affected by the sequence context of their TEPs, suggesting that the regulatory elements of TEPs could control the transcription level in additional layers. We also identified TU features of a xenobiotic response element (XRE) family regulator and DUF397 domain-containing protein, particularly showing the abundance of bidirectional TEPs. Finally, we found that 189 noncoding TUs contained potential cis- and trans-regulatory elements that played a major role in regulating the 5' and 3' UTR. These findings highlight the role of transcriptional regulatory elements in transcription termination and posttranscriptional processing in Streptomyces sp.IMPORTANCEStreptomyces sp. is a great source of bioactive secondary metabolites, including antibiotics, antifungal agents, antiparasitic agents, immunosuppressant compounds, and other drugs. Secondary metabolites are synthesized via multistep conversions of the precursor molecules from primary metabolism, governed by multicomplex enzymes from secondary metabolite biosynthetic gene clusters. As their production is closely related with the growth phase and dynamic cellular status in response to various intra- and extracellular signals, complex regulatory systems tightly control the gene expressions related to secondary metabolism. In this study, we determined genome-wide transcript 3'-end positions and transcription units in the β-lactam antibiotic producer Streptomyces clavuligerus ATCC 27064 to elucidate the transcriptional regulatory elements in transcription termination and posttranscriptional processing by integration of multiomics data. These unique features, such as transcript 3'-end sequence, potential riboregulators, and potential 3'-untranslated region (UTR) cis-regulatory elements, can be potentially used to design engineering tools that can regulate the transcript abundance of genes for enhancing secondary metabolite production.

Streptomyces species are gram-positive bacteria with GC-rich linear genomes and they serve as dominant reservoirs for producing clinically and industrially important secondary metabolites. Genome mining of Streptomyces revealed that each Streptomyces species typically encodes 20-50 secondary metabolite biosynthetic gene clusters (smBGCs), emphasizing their potential for novel compound discovery. Unfortunately, most of smBGCs are uncharacterized in terms of their products and regulation since they are silent under laboratory culture conditions. To translate the genomic potential of Streptomyces to practical applications, it is essential to understand the complex regulation of smBGC expression and to identify the underlying regulatory elements. To progress towards these goals, we applied two Next-Generation Sequencing methods, dRNA-Seq and Term-Seq, to industrially relevant Streptomyces species to reveal the 5´ and 3´ boundaries of RNA transcripts on a genome scale. This data provides a fundamental resource to aid our understanding of Streptomyces' regulation of smBGC expression and to enhance their potential for secondary metabolite synthesis.

Determining transcriptional and translational regulatory elements in GC-rich Streptomyces genomes is essential to elucidating the complex regulatory networks that govern secondary metabolite biosynthetic gene cluster (BGC) expression. However, information about such regulatory elements has been limited for Streptomyces genomes. To address this limitation, a high-quality genome sequence of β-lactam antibiotic-producing Streptomyces clavuligerus ATCC 27 064 is completed, which contains 7163 newly annotated genes. This provides a fundamental reference genome sequence to integrate multiple genome-scale data types, including dRNA-Seq, RNA-Seq and ribosome profiling. Data integration results in the precise determination of 2659 transcription start sites which reveal transcriptional and translational regulatory elements, including -10 and -35 promoter components specific to sigma (σ) factors, and 5'-untranslated region as a determinant for translation efficiency regulation. Particularly, sequence analysis of a wide diversity of the -35 components enables us to predict potential σ-factor regulons, along with various spacer lengths between the -10 and -35 elements. At last, the primary transcriptome landscape of the β-lactam biosynthetic pathway is analyzed, suggesting temporal changes in metabolism for the synthesis of secondary metabolites driven by transcriptional regulation. This comprehensive genetic information provides a versatile genetic resource for rational engineering of secondary metabolite BGCs in Streptomyces.

Objective: To determine age-related risk factors for chronic rhinosinusitis (CRS) with asthma. Methods: Data were obtained from a national survey of non-hospitalized civilians conducted by the Korean Center for Disease Control and Prevention. CRS diagnosis was based on the guidelines of the European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Asthma was judged based on whether the patient had been diagnosed with asthma in the past. Of the 45,811 survey participants, 26,335 were included in the cross-sectional study. Participants included in the study were divided into the control, CRS, and CRS with asthma groups. Age-related risk factors were analyzed in patients aged < 60 or > 60 years. Univariate logistic analyses were performed to evaluate the relationship between groups. Risk factors included age, sex, household income, residence, education level, occupation, and body mass index (BMI). Results: Education level (Odds Ratio [OR]: 0.342, P =.0003), BMI (OR: 1.09, P =.0082), and total IgE (TIgE) levels (OR: 5.582, P =.003) were significantly different between the control and the CRS with asthma group. Education level (OR: 0.478, P =.0016) and TIgE levels (OR: 4, P =.0218) were significantly different between the CRS and CRS with asthma groups under 60 years of age. BMI (OR: 1.087, P =.0443; OR: 1.104, P =.0224) showed a significant difference between all three groups with age > 60 years. Conclusion: Progression to CRS with asthma is influenced by education level, occupation, and TIgE levels in patients under 60 years of age. BMI was the only influencing factor associated with the progression to CRS with asthma in those aged > 60 years. [ABSTRACT FROM AUTHOR]