Hang Wu

Hang Wu
Anhui University · School of Life Sciences

Ph.D.

About

36
Publications
3,347
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471
Citations
Citations since 2017
19 Research Items
386 Citations
2017201820192020202120222023020406080
2017201820192020202120222023020406080
2017201820192020202120222023020406080
2017201820192020202120222023020406080

Publications

Publications (36)
Article
Full-text available
TetR family transcriptional regulators (TFRs) are widespread in actinomycetes, which exhibit diverse regulatory modes in antibiotic biosynthesis. Nitrogen regulators play vital roles in modulation of primary and secondary metabolism. However, crosstalk between TFR and nitrogen regulator has rarely been reported in actinomycetes. Herein, we demonstr...
Preprint
The transcription factor (TF)-mediated regulatory network controlling lincomycin production in Streptomyces lincolnensis is yet to be fully elucidated despite several types of associated TFs having been reported. SLCG_2919, a tetracycline repressor (TetR)-type regulator, was the first TF to be characterized outside the lincomycin biosynthetic clust...
Article
Full-text available
Numerous antibiotics are derived from polyketides, whose biosynthesis is accurately controlled by transcriptional regulators that respond to diverse physiological or environmental signals. It is generally accepted that antibiotics or biosynthetic intermediates serve as effectors to modulate their production in actinomycetes.
Article
Full-text available
Erythromycins produced by Saccharopolyspora erythraea have broad-spectrum antibacterial activities. Recently, several TetR-family transcriptional regulators (TFRs) were identified to control erythromycin production by multiplex control modes; however, their regulatory network remains poorly understood. In this study, we report a novel TFR, SACE_030...
Article
TetR family transcriptional regulators (TFRs) are widely distributed in bacteria and archaea, and the first discovered TFR was confirmed to control the expression of tetracycline efflux pump in Escherichia coli. TFRs can bind DNAs and ligands. Small molecule ligands can induce conformational changes of TFRs, inhibiting or promoting TFRs to control...
Article
Full-text available
The Lrp and MarR families are two groups of transcriptional regulators widely distributed among prokaryotes. However, the hierarchical-regulatory relationship between the Lrp family and the MarR family remains unknown. Our previous study found that an Lrp (SACE_Lrp) from Saccharopolyspora erythraea indirectly repressed the biosynthesis of erythromy...
Article
Full-text available
DNA damage and epigenetic marks are well established to have profound influences on genome stability and cell phenotype, yet there are few technologies to obtain high-resolution genomic maps of the many types of chemical modifications of DNA. Here we present Nick-seq for quantitative, sensitive, and accurate mapping of DNA modifications at single-n...
Article
Full-text available
Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in Streptomyces lincolnensis, identified an Lrp (named as SL...
Preprint
Here we present the Nick-seq platform for quantitative mapping of DNA modifications and damage at single-nucleotide resolution across genomes. Pre-existing breaks are blocked and DNA structures converted to strand-breaks for 3'-extension by nick-translation to produce nuclease-resistant oligonucleotides, and 3'-capture by terminal transferase taili...
Article
The regulatory mechanism of lincomycin biosynthesis remains largely unknown, although lincomycin and its derivatives have been of great application in pharmaceutical industry. As a global regulator, BldD is widespread in Streptomyces, and functions as an on-off switch to regulate the transition from morphological differentiation to secondary metabo...
Article
Full-text available
In this work, we found that the Lrp/AsnC family protein SACE_5717 negatively regulated erythromycin biosynthesis in S. erythraea. Disruption of SACE_5717 led to a 27% improvement in the yield of erythromycin in S. erythraea A226. SACE_5717 directly repressed its own gene expression, as well as that of the adjacent gene SACE_5716 by binding to the t...
Article
Full-text available
Background Erythromycin A (Er-A) produced by the actinomycete Saccharopolyspora erythraea is an important antibiotic extensively used in human medicine. Dissecting of transcriptional regulators and their target genes associated with erythromycin biosynthesis is crucial to obtain erythromycin overproducer strains through engineering of relevant regu...
Article
Full-text available
TetR family transcriptional regulators (TFRs) are generally found to regulate diverse cellular processes in bacteria, especially antibiotic biosynthesis in Streptomyces species. However, knowledge of their function in lincomycin biosynthesis in S. lincolnensis remains unknown. The present study provides a new insight into the regulation of lincomyc...
Article
In the online published article, row value "pIB139-metK1-metK2" in table 1 has been processed incorrectly. The correct table is given below.
Article
Streptomyces lincolnensis is generally utilized for the production of lincomycin A (Lin-A), a clinically useful antibiotic to treat Gram-positive bacterial infections. Three methylation steps, catalyzed by three different S-adenosylmethionine (SAM)-dependent methyltransferases, are required in the biosynthesis of Lin-A, and thus highlight the signi...
Article
Full-text available
Nitrate is necessary for primary and secondary metabolism of actinomycetes and stimulates the production of a few antibiotics, such as lincomycin and rifamycin. However, the mechanism of this nitrate-stimulating effect was not fully understood. Two putative ABC-type nitrate transporters were identified in Streptomyces lincolnensis NRRL2936 and veri...
Article
Full-text available
Lrp/AsnC family regulators have been found in many bacteria as crucial regulators controlling diverse cellular processes. By genomic alignment, we found that SCO3361, an Lrp/AsnC family protein from Streptomyces coelicolor, shared the highest similarity to the SACE_Lrp from Saccharopolyspora erythraea. Deletion of SCO3361 led to dramatic reduction...
Article
Full-text available
Giant linear plasmids, which replicate independently of the chromosomes, widely exist in actinobacteria. Previous studies mostly focused on the replication and evolution of the linear plasmids or the secondary metabolite gene clusters and the resistance gene clusters therein. However, the relationships of the linear plasmids to the productivities o...
Article
Leucine-responsive regulatory proteins (Lrps) are a group of transcriptional regulators that regulate diverse cellular processes in bacteria and archaea. However, the regulatory role of Lrps in antibiotic biosynthesis remains poorly understood. In this study, we show that SACE_5388, an Lrp family regulator named as SACE_Lrp, is an efficient regulat...
Article
Full-text available
Glycosyltransferase DesVII and its auxiliary partner DesVIII from Streptomyces venezulae, homologs of EryCIII and EryCII in Saccharopolyspora erythraea, have previously been demonstrated to be flexible on their substrates in vitro. Herein, we investigated their in vivo function by interspecies complementation in the mutant strains of Sac. erythraea...
Article
Full-text available
Erythromycin A is a widely used antibiotic produced by Saccharopolyspora erythraea; however, its biosynthetic cluster lacks a regulatory gene, limiting the yield enhancement via regulation engineering of S. erythraea. Herein, six TetR family transcriptional regulators (TFRs) belonging to three genomic context types were individually inactivated in...
Article
Clostridium butyricum is an important fragrance-producing bacterium in the traditional Chinese flavor liquor-making industry. Here the complete genome sequence of C. butyricum JKY6D1 isolated from the pit mud of a Chinese flavor liquor-making factory is presented. The genome is 4,618,327 bp with the GC content of 28.74% and a plasmid of 8060 bp. Th...
Article
BldD (SACE_2077), a key developmental regulator in actinomycetes, is the first identified transcriptional factor in Saccharopolyspora erythraea positively regulating erythromycin production and morphological differentiation. Although the BldD of S. erythraea binds to the promoters of erythromycin biosynthetic genes, the interaction affinities are r...
Article
Validamycin A (VAL-A) is a C7N aminocyclitol antibiotic produced by Streptomyces hygroscopicus var. jinggangensis 5008, which has been widely used as antifungal agent against rice sheath blight disease. VAL-A biosynthesis has been proven to be affected by γ-butyrolactone and temperature. Herein, we showed that GlnR, a global regulator in nitrogen m...
Article
Full-text available
Background: Saccharopolyspora erythraea was extensively utilized for the industrial-scale production of erythromycin A (Er-A), a macrolide antibiotic commonly used in human medicine. Yet, S. erythraea lacks regulatory genes in the erythromycin biosynthetic gene (ery) cluster, hampering efforts to enhance Er-A production via the engineering of regu...
Article
Erythromycin, a medically important antibiotic, is produced by Saccharopolyspora erythraea. Unusually, the erythromycin biosynthetic gene cluster lacks a regulatory gene, and the regulation of its biosynthesis remains largely unknown. In this study, through gene deletion, complementation and overexpression experiments, we identified a novel TetR fa...
Article
Cyclothiazomycin is a member of the thiopeptide antibiotics, which are usually complicated derivatives of ribosomally synthesized peptides. A gene cluster containing twelve open reading frames identical to the clt cluster encoding cyclothiazomycin from Streptomyces hygroscopicus 10-22 was revealed by genome sequencing in Streptomyces hygroscopicus...
Article
To investigate the role of lincomycin transporter LmrC in lincomycin biosynthesis, lmrC was deleted in a lincomycin high-yielding strain LC-G by homologous recombination. HPLC analysis and resistance assay indicated that lincomycin production and self-resistance in XJJ7, and the lmrC mutant were decreased by 55% and 50%, respectively. Quantitative...
Article
Full-text available
Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptiona...
Article
Microbial drugs are secondary metabolites with diverse structures and bioactivities. In recent years, considerable genomes of the drug-producing microorganisms have been completely sequenced. Subsequently, functional genomic studies have been performed, which shed new lights on anibiotic biosynthesis, morphological differentiation, regulation, phyl...
Article
Full-text available
Streptomyces hygroscopicus 5008 has been used for the production of the antifungal validamycin/jinggangmycin for more than 40 years. A high yield of validamycin is achieved by culturing the strain at 37°C, rather than at 30°C for normal growth and sporulation. The mechanism(s) of its thermo-regulated biosynthesis was largely unknown. The 10,383,684...
Article
Actinomycete species from many genera often harbor linear plasmids and some contain linear chromosomes. A self-ligation and PCR-sequencing method was developed for identifying three novel telomere sequences of linear plasmids of Streptomyces and Mycobacterium. This and four previously described methods for actinomycetes telomere cloning and sequenc...
Article
Full-text available
In order to enhance the production of validamycin A (VAL-A), a widely used agricultural antibiotic, a temperature shift strategy was developed in the fermentation of Streptomyces hygroscopicus 5008. VAL-A production and the transcriptional levels of its structural genes were enhanced in the optimal temperature shift condition. The addition of diphe...
Article
During the fermentation of Streptomyces hygroscopicus TL01 to produce validamycin A (18 g/L), a considerable amount of an intermediate validoxylamine A (4.0 g/L) is accumulated. Chemical or enzymatic hydrolysis of validamycin A was not observed during the fermentation process. Over-expression of glucosyltransferase ValG in TL01 did not increase the...
Article
γ-Butyrolactone autoregulator produced in Streptomyces is a low-molecular-weight compound controlling secondary metabolism and morphological differentiation in Streptomyces. Based on minor structural difference in the C-2 side chain, these autoregulators chemically identified to date can be classified into three types: the A-factor type, the virgin...
Article
The eryA genes play a very important role in the biosynthesis of erythromycin macrolactone ring (6-deoxy-erythronolide B, 6-dEB). In this paper, an Escherichia coli-Saccharopolyspora erythraea shuttle vector containing the eryA promoter region was constructed using the enhanced green fluorescent protein (EGFP) gene as a reporter. The shuttle plasmi...

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