scholarly journals Regulatory Patterns of Crp on Monensin Biosynthesis in Streptomyces cinnamonensis

2020 ◽  
Vol 8 (2) ◽  
pp. 271
Author(s):  
Chun-Yan Lin ◽  
Yue Zhang ◽  
Ji-Hua Wu ◽  
Rong-Hui Xie ◽  
Jianjun Qiao ◽  
...  
Keyword(s):  
Regulatory Gene ◽  
Biosynthetic Gene Cluster ◽  
Receptor Protein ◽  
Sequencing Analysis ◽  
Positive Role ◽  
Agricultural Industry ◽  
Metabolic Genes ◽  
Streptomyces Cinnamonensis ◽  
Malonyl Coa ◽  
Regulatory Effects

Monensin, produced by Streptomyces cinnamonensis, is a polyether ionophore antibiotic widely used as a coccidiostat and a growth-promoting agent in agricultural industry. In this study, cyclic AMP receptor protein (Crp), the global transcription factor for regulation of monensin biosynthesis, was deciphered. The overexpression and antisense RNA silencing of crp revealed that Crp plays a positive role in monensin biosynthesis. RNA sequencing analysis indicated that Crp exhibited extensive regulatory effects on genes involved in both primary metabolic pathways and the monensin biosynthetic gene cluster (mon). The primary metabolic genes, including acs, pckA, accB, acdH, atoB, mutB, epi and ccr, which are pivotal in the biosynthesis of monensin precursors malonyl-CoA, methylmalonyl-CoA and ethylmalonyl-CoA, are transcriptionally upregulated by Crp. Furthermore, Crp upregulates the expression of most mon genes, including all PKS genes (monAI to monAVIII), tailoring genes (monBI-monBII-monCI, monD and monAX) and a pathway-specific regulatory gene (monRI). Enhanced precursor supply and the upregulated expression of mon cluser by Crp would allow the higher production of monensin in S. cinnamonensis. This study gives a more comprehensive understanding of the global regulator Crp and extends the knowledge of Crp regulatory mechanism in Streptomyces.

scholarly journals Improvement of Nemadectin Production by Overexpressing the Regulatory Gene nemR and Nemadectin Biosynthetic Gene Cluster in Streptomyces Cyaneogriseus

2021 ◽  
Author(s):  
Yuan-Jie Wu ◽  
Song-Bai Yang ◽  
Zheng-Yu Zhang ◽  
Shao-Xin Chen
Keyword(s):  
Gene Cluster ◽  
Wild Type Strain ◽  
Regulatory Gene ◽  
Anthelmintic Activity ◽  
Biosynthetic Gene Cluster ◽  
Wild Type ◽  
Transcription Level ◽  
Positive Role ◽  
C 23 ◽  
In The Wild

AbstractNemadectin, a 16-member macrocyclic lactone antiparasitic antibiotic, is produced by Streptomyces cyaneogriseus subspecies noncyanogenus. Moxidectin, a C-23 oximate derivative of nemadectin, is widely used as a pesticide due to its broad-spectrum, highly efficient, and safe anthelmintic activity. NemR, a LAL family regulator, is encoded by nemR and is involved in nemadectin biosynthesis in S. cyaneogriseus. In this report, gene disruption and complementation experiments showed that nemR plays a positive role in the biosynthesis of nemadectin. The transcription level of nemadectin biosynthetic genes in the nemR knockout strain was significantly decreased compared with those in the wild-type strain MOX-101. However, overexpression of nemR under the control of native or strong constitutive promoters resulted in the opposite, increasing the production of nemadectin by 56.5 or 73.5%, respectively, when compared with MOX-101. In addition, the gene cluster of nemadectin biosynthesis was further cloned and overexpressed using a CRISPR method, which significantly increase nemadectin yield by 108.6% (509 mg/L) when compared with MOX-101.

scholarly journals New Insights into the Genetic Organization of the FK228 Biosynthetic Gene Cluster inChromobacterium violaceumNo. 968

2010 ◽  
Vol 77 (4) ◽  
pp. 1508-1511 ◽  
Author(s):  
Vishwakanth Y. Potharla ◽  
Shane R. Wesener ◽  
Yi-Qiang Cheng
Keyword(s):  
Natural Product ◽  
Gene Cluster ◽  
Gene Deletion ◽  
Regulatory Gene ◽  
Biosynthetic Gene Cluster ◽  
Transcriptional Analysis ◽  
Biosynthetic Gene ◽  
Genetic Organization

ABSTRACTThe biosynthetic gene cluster of FK228, an FDA-approved anticancer natural product, was identified and sequenced previously. The genetic organization of this gene cluster has now been delineated through systematic gene deletion and transcriptional analysis. As a result, the gene cluster is redefined to contain 12 genes:depAthroughdepJ,depM, and a newly identified pathway regulatory gene,depR.

scholarly journals Characterization of the Noncanonical Regulatory and Transporter Genes in Atratumycin Biosynthesis and Production in a Heterologous Host

Marine Drugs ◽  
2019 ◽  
Vol 17 (10) ◽  
pp. 560 ◽  
Author(s):  
Zhijie Yang ◽  
Xin Wei ◽  
Jianqiao He ◽  
Changli Sun ◽  
Jianhua Ju ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Streptomyces Coelicolor ◽  
Regulatory Gene ◽  
Regulatory Protein ◽  
Biosynthetic Gene Cluster ◽  
Negative Regulator ◽  
Over Expression ◽  
Lead Compounds ◽  
Mycobacteria Tuberculosis ◽  
Abc Transporter Genes

Atratumycin is a cyclodepsipeptide with activity against Mycobacteria tuberculosis isolated from deep-sea derived Streptomyces atratus SCSIO ZH16NS-80S. Analysis of the atratumycin biosynthetic gene cluster (atr) revealed that its biosynthesis is regulated by multiple factors, including two LuxR regulatory genes (atr1 and atr2), two ABC transporter genes (atr29 and atr30) and one Streptomyces antibiotic regulatory gene (atr32). In this work, three regulatory and two transporter genes were unambiguously determined to provide positive, negative and self-protective roles during biosynthesis of atratumycin through bioinformatic analyses, gene inactivations and trans-complementation studies. Notably, an unusual Streptomyces antibiotic regulatory protein Atr32 was characterized as a negative regulator; the function of Atr32 is distinct from previous studies. Five over-expression mutant strains were constructed by rational application of the regulatory and transporter genes; the resulting strains produced significantly improved titers of atratumycin that were ca. 1.7–2.3 fold greater than wild-type (WT) producer. Furthermore, the atratumycin gene cluster was successfully expressed in Streptomyces coelicolor M1154, thus paving the way for the transfer and recombination of large DNA fragments. Overall, this finding sets the stage for understanding the unique biosynthesis of pharmaceutically important atratumycin and lays the foundation for generating anti-tuberculosis lead compounds possessing novel structures.

scholarly journals Enhanced Heterologous Production of Desosaminyl Macrolides and Their Hydroxylated Derivatives by Overexpression of the pikD Regulatory Gene in Streptomyces venezuelae

2008 ◽  
Vol 74 (7) ◽  
pp. 1972-1979 ◽  
Author(s):  
Won Seok Jung ◽  
Soon Jeong Jeong ◽  
Sung Ryeol Park ◽  
Cha Yong Choi ◽  
Byoung Chul Park ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Regulatory Gene ◽  
Biosynthetic Gene Cluster ◽  
Vector System ◽  
Heterologous Production ◽  
Streptomyces Venezuelae ◽  
Positive Regulator ◽  
Enhanced Production ◽  
Notable Increase

ABSTRACT To elevate the production level of heterologous polyketide in Streptomyces venezuelae, an additional copy of the positive regulatory gene pikD was introduced into the pikromycin (Pik) polyketide synthase (PKS) deletion mutant of S. venezuelae ATCC 15439 expressing tylosin PKS genes. The resulting mutant strain showed enhanced production of both tylactone (TL) and desosaminyl tylactone (DesTL) of 2.7- and 17.1-fold, respectively. The notable increase in DesTL production strongly suggested that PikD upregulates the expression of the desosamine (des) biosynthetic gene cluster. In addition, two hydroxylated forms of DesTL were newly detected from the extract of this mutant. These hydroxylated forms presumably resulted from a PikD-dependent increase in expression of the pikC gene that encodes P450 hydroxylase. Gene expression analysis by reverse transcriptase PCR and bioconversion experiments of 10-deoxymethynolide, narbonolide, and TL into the corresponding desosaminyl macrolides indicated that PikD is a positive regulator of the des and pikC genes, as well as the Pik PKS genes. These results demonstrate the role of PikD as a pathway-specific positive regulator of the entire Pik biosynthetic pathway and its usefulness in the development of a host-vector system for efficient heterologous production of desosaminyl macrolides and novel hydroxylated compounds.

scholarly journals The Pseudomonas chlororaphis PCL1391 Sigma Regulator psrA Represses the Production of the Antifungal Metabolite Phenazine-1-Carboxamide

2005 ◽  
Vol 18 (3) ◽  
pp. 244-253 ◽  
Author(s):  
Thomas F. C. Chin-A-Woeng ◽  
Daan van den Broek ◽  
Ben J. J. Lugtenberg ◽  
Guido V. Bloemberg
Keyword(s):  
Quorum Sensing ◽  
Regulatory Gene ◽  
Regulatory System ◽  
Homoserine Lactone ◽  
Biosynthetic Gene Cluster ◽  
Phytopathogenic Fungus ◽  
Pseudomonas Chlororaphis ◽  
Antifungal Metabolite ◽  
Expression Studies ◽  
Multiple Copies

The rhizobacterium Pseudomonas chlororaphis PCL1391 produces the antifungal metabolite phenazine-1-carboxamide (PCN), which is a crucial trait in its competition with the phytopathogenic fungus Fusarium oxysporum f. sp. radicis-lycopersici in the rhizosphere. The expression of the PCN biosynthetic gene cluster in PCL1391 is population density-dependent and is regulated by the quorum-sensing genes phzI and phzR via synthesis of the autoinducer Nhexanoyl-L-homoserine lactone (C6-HSL). Here, we describe the identification of an additional regulatory gene of PCN biosynthesis in PCL1391. A mutation in the psrA gene (Pseudomonas sigma regulator), the gene product of which is a member of the TetR/AcrR family of transcriptional regulators, resulted in increased production of autoinducer molecules and PCN. Expression studies showed that inactivation of psrA resulted in increased expression of the phzI and phzR genes and the phz biosynthetic operon and that introduction of functional copies of psrA represses the expression of these genes, resulting in reduced production of autoinducer signal and PCN. Surprisingly, inactivation of psrA in the phzI or phzR quorum-sensing mutants, which do not produce detectable amounts of PCN and autoinducers by themselves, restored PCN biosynthesis. This phenomenon was accompanied by the appearance of compounds with autoinducer activities migrating at the positions of C4-HSL and C6-HSL on C18 reverse phase-thin-layer chromatography. These observations indicate that PsrA also represses at least one silent, yet unidentified, quorum-sensing system or autoinducer biosynthetic pathway in PCL1391. The expression of psrA declines at the onset of the stationary phase at the same moment at which quorum-sensing (-regulated) genes are activated. In addition, expression studies in a psrA- and a multicopy psrA background showed that psrA is autoregulated. Multiple copies of psrA repress its own expression. Mutation of gacS, encoding the sensor kinase member of a two-component global regulatory system significantly reduced production of autoinducers and PCN. We show a novel link between global regulation and quorum sensing via the PsrA regulator.

scholarly journals Comparative transcriptomic analyses of glucosinolate metabolic genes during the formation of Chinese kale seeds

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yijiao Zhao ◽  
Zeyuan Chen ◽  
Jiaxuan Chen ◽  
Bingxing Chen ◽  
Weiling Tang ◽  
...  
Keyword(s):  
Transcriptome Sequencing ◽  
Sequencing Analysis ◽  
Biosynthetic Genes ◽  
Seed Formation ◽  
Catabolic Enzymes ◽  
Metabolic Genes ◽  
Chinese Kale ◽  
Transcriptomic Sequencing ◽  
Embryo Stage ◽  
Two Stages

Abstract Background To understand the mechanism of glucosinolates (GSs) accumulation in the specific organs, combined analysis of physiological change and transcriptome sequencing were applied in the current study. Taking Chinese kale as material, seeds and silique walls were divided into different stages based on the development of the embryo in seeds and then subjected to GS analysis and transcriptome sequencing. Results The main GS in seeds of Chinese kale were glucoiberin and gluconapin and their content changed with the development of the seed. During the transition of the embryo from torpedo- to the early cotyledonary-embryo stage, the accumulation of GS in the seed was accompanied by the salient decline of GS in the corresponding silique wall. Thus, the seed and corresponding silique wall at these two stages were subjected to transcriptomic sequencing analysis. 135 genes related to GS metabolism were identified, of which 24 genes were transcription factors, 81 genes were related to biosynthetic pathway, 25 genes encoded catabolic enzymes, and 5 genes matched with transporters. The expression of GS biosynthetic genes was detected both in seeds and silique walls. The high expression of FMOGS-OX and AOP2, which is related to the production of gluconapin by side modification, was noted in seeds at both stages. Interestingly, the expression of GS biosynthetic genes was higher in the silique wall compared with that in the seed albeit lower content of GS existed in the silique wall than in the seed. Combined with the higher expression of transporter genes GTRs in silique walls than in seeds, it was proposed that the transportation of GS from the silique wall to the seed is an important source for seed GS accumulation. In addition, genes related to GS degradation expressed abundantly in the seed at the early cotyledonary-embryo stage indicating its potential role in balancing seed GS content. Conclusions Two stages including the torpedo-embryo and the early cotyledonary-embryo stage were identified as crucial in GS accumulation during seed development. Moreover, we confirmed the transportation of GS from the silique wall to the seed and proposed possible sidechain modification of GS biosynthesis may exist during seed formation.

scholarly journals Silencing and Transcriptional Regulation of Endogenous Retroviruses: An Overview

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 884 ◽  
Author(s):  
Franziska K. Geis ◽  
Stephen P. Goff
Keyword(s):  
Posttranslational Modifications ◽  
Binding Sites ◽  
Germ Line ◽  
Regulatory Gene ◽  
Endogenous Retroviruses ◽  
Gene Products ◽  
Positive Role ◽  
Master Regulators ◽  
H3k9 Trimethylation ◽  
Cancer Types

Almost half of the human genome is made up of transposable elements (TEs), and about 8% consists of endogenous retroviruses (ERVs). ERVs are remnants of ancient exogenous retrovirus infections of the germ line. Most TEs are inactive and not detrimental to the host. They are tightly regulated to ensure genomic stability of the host and avoid deregulation of nearby gene loci. Histone-based posttranslational modifications such as H3K9 trimethylation are one of the main silencing mechanisms. Trim28 is one of the identified master regulators of silencing, which recruits most prominently the H3K9 methyltransferase Setdb1, among other factors. Sumoylation and ATP-dependent chromatin remodeling factors seem to contribute to proper localization of Trim28 to ERV sequences and promote Trim28 interaction with Setdb1. Additionally, DNA methylation as well as RNA-mediated targeting of TEs such as piRNA-based silencing play important roles in ERV regulation. Despite the involvement of ERV overexpression in several cancer types, autoimmune diseases, and viral pathologies, ERVs are now also appreciated for their potential positive role in evolution. ERVs can provide new regulatory gene elements or novel binding sites for transcription factors, and ERV gene products can even be repurposed for the benefit of the host.

scholarly journals A bacterial hormone (the SCB1) directly controls the expression of a pathway-specific regulatory gene in the cryptic type I polyketide biosynthetic gene cluster of Streptomyces coelicolor

2005 ◽  
Vol 56 (2) ◽  
pp. 465-479 ◽  
Author(s):  
Eriko Takano ◽  
Hiroshi Kinoshita ◽  
Vassilis Mersinias ◽  
Giselda Bucca ◽  
Graham Hotchkiss ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Streptomyces Coelicolor ◽  
Regulatory Gene ◽  
Biosynthetic Gene Cluster ◽  
Type I ◽  
Biosynthetic Gene ◽  
Polyketide Biosynthetic Gene Cluster

scholarly journals Alpha-lipoic acid protects against pressure overload-induced heart failure via ALDH2-dependent Nrf1-FUNDC1 signaling

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Wenjia Li ◽  
Lei Yin ◽  
Xiaolei Sun ◽  
Jian Wu ◽  
Zhen Dong ◽  
...  
Keyword(s):  
Heart Failure ◽  
Lipoic Acid ◽  
Pressure Overload ◽  
Diabetic Animal ◽  
Neonatal Rat ◽  
Receptor Protein ◽  
Alpha Lipoic Acid ◽  
Wild Type ◽  
Positive Role ◽  
Rat Cardiomyocytes

Abstract Alpha-lipoic acid (α-LA), a well-known antioxidant, was proved to active ALDH2 in nitrate tolerance and diabetic animal model. However, the therapeutic advantage of α-LA for heart failure and related signaling pathway have not been explored. This study was designed to examine the role of α-LA–ALDH2 in heart failure injury and mitochondrial damage. ALDH2 knockout (ALDH2−/−) mice and primary neonatal rat cardiomyocytes (NRCMs) were subjected to assessment of myocardial function and mitochondrial autophagy. Our data demonstrated α-LA significantly reduced the degree of TAC-induced LV hypertrophy and dysfunction in wild-type mice, not in ALDH2−/− mice. In molecular level, α-LA significantly restored ALDH2 activity and expression as well as increased the expression of a novel mitophagy receptor protein FUNDC1 in wild-type TAC mice. Besides, we confirmed that ALDH2 which was activated by α-LA governed the activation of Nrf1–FUNDC1 cascade. Our data suggest that α-LA played a positive role in protecting the heart against adverse effects of chronic pressure overload.

scholarly journals Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization

2003 ◽  
Vol 49 (5) ◽  
pp. 1179-1190 ◽  
Author(s):  
Markiyan Oliynyk ◽  
Christian B. W. Stark ◽  
Apoorva Bhatt ◽  
Michelle A. Jones ◽  
Zoë A. Hughes-Thomas ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Oxidative Cyclization ◽  
Biosynthetic Gene ◽  
Streptomyces Cinnamonensis
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