AaWRKY4 upregulates artemisinin content through boosting the expressions of key enzymes in artemisinin biosynthetic pathway

Background: Antibiotic resistance is currently a serious problem for global public health. To this end, discovery of new antibacterial drugs that interact with novel targets is important. The biosynthesis of lipoproteins is vital to bacterial survival and its inhibitors have shown efficacy against a range of bacteria, thus bacterial lipoprotein biosynthetic pathway is a potential target. Methods: At first, the literature that covered the basic concept of bacterial lipoprotein biosynthetic pathway as well as biochemical characterization of three key enzymes was reviewed. Then, the recently resolved crystal structures of the three enzymes were retrieved from Protein Data Bank (PDB) and the essential residues in the active sites were analyzed. Lastly, all the available specific inhibitors targeting this pathway and their Structure-activity Relationship (SAR) were discussed. Results: We briefly introduce the bacterial lipoprotein biosynthetic pathway and describe the structures and functions of three key enzymes in detail. In addition, we present much knowledge on ligand recognition that may facilitate structure-based drug design. Moreover, we focus on the SAR of LspA inhibitors and discuss their potency and drug-likeness. Conclusion: This review presents a clear background of lipoprotein biosynthetic pathway and provides practical clues for structure-based drug design. In particular, the most up-to-date knowledge on the SAR of lead compounds targeting this pathway would be a good reference for discovery of a novel class of antibacterial agents.

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Abscisic acid (ABA) treatment increases artemisinin content in Artemisia annua by enhancing the expression of genes in artemisinin biosynthetic pathway

Biologia ◽

10.2478/s11756-009-0040-8 ◽

2009 ◽

Vol 64 (2) ◽

Cited By ~ 56

Author(s):

Fuyuan Jing ◽

Ling Zhang ◽

Meiya Li ◽

Yueli Tang ◽

Yuliang Wang ◽

...

Keyword(s):

Abscisic Acid ◽

Cell Suspension ◽

Biosynthetic Pathway ◽

Gene Expression Analysis ◽

Artemisia Annua ◽

Cell Suspension Cultures ◽

Dry Weight ◽

Suspension Cultures ◽

Expression Of Genes ◽

Artemisinin Content

AbstractArtemisinin, a sesquiterpene lactone endoperoxide derived from Artemisia annua L., is the most effective antimalarial drug. In an effort to increase the artemisinin production, abscisic acid (ABA) with different concentrations (1, 10 and 100 µM) was tested by treating A. annua plants. As a result, the artemisinin content in ABA-treated plants was significantly increased. Especially, artemisinin content in plants treated by 10 µM ABA was 65% higher than that in the control plants, up to an average of 1.84% dry weight. Gene expression analysis showed that in both the ABA-treated plants and cell suspension cultures, HMGR, FPS, CYP71AV1 and CPR, the important genes in the artemisinin biosynthetic pathway, were significantly induced. While only a slight increase of ADS expression was observed in ABA-treated plants, no expression of ADS was detected in cell suspension cultures. This study suggests that there is probably a crosstalk between the ABA signaling pathway and artemisinin biosynthetic pathway and that CYP71AV1, which was induced most significantly, may play a key regulatory role in the artemisinin biosynthetic pathway.

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Rhizophagus intraradices or its associated bacteria affect gene expression of key enzymes involved in the rosmarinic acid biosynthetic pathway of basil

Mycorrhiza ◽

10.1007/s00572-016-0707-2 ◽

2016 ◽

Vol 26 (7) ◽

pp. 699-707 ◽

Cited By ~ 25

Author(s):

Fabio Battini ◽

Rodolfo Bernardi ◽

Alessandra Turrini ◽

Monica Agnolucci ◽

Manuela Giovannetti

Keyword(s):

Gene Expression ◽

Rosmarinic Acid ◽

Biosynthetic Pathway ◽

Associated Bacteria ◽

Key Enzymes ◽

Rhizophagus Intraradices ◽

Affect Gene Expression

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Enhancing menaquinone-7 production in recombinant Bacillus amyloliquefaciens by metabolic pathway engineering

RSC Advances ◽

10.1039/c7ra03388e ◽

2017 ◽

Vol 7 (45) ◽

pp. 28527-28534 ◽

Cited By ~ 14

Author(s):

Jian-Zhong Xu ◽

Wei-Liu Yan ◽

Wei-Guo Zhang

Keyword(s):

Enzyme Activity ◽

Metabolic Pathway ◽

Bacillus Amyloliquefaciens ◽

Biosynthetic Pathway ◽

Pathway Engineering ◽

Key Enzymes ◽

Metabolic Pathway Engineering ◽

High Enzyme ◽

High Enzyme Activity

Six key enzymes are vital for MK-7 production, but the same enzyme has different effect on MK-7 production in different cultivating methods. Thus, the high enzyme activity and high-traffic biosynthetic pathway are beneficial to synthesize MK-7.

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Genome-Wide Analysis of Alternative Splicing and Non-Coding RNAs Reveal Complicated Transcriptional Regulation in Cannabis sativa L.

International Journal of Molecular Sciences ◽

10.3390/ijms222111989 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11989

Author(s):

Bin Wu ◽

Yanni Li ◽

Jishuang Li ◽

Zhenzhen Xie ◽

Mingbao Luan ◽

...

Keyword(s):

Gene Expression ◽

Alternative Splicing ◽

Biosynthetic Pathway ◽

Cannabis Sativa ◽

Transcriptional Level ◽

Gene Expression And Regulation ◽

Structural Genes ◽

Key Enzymes ◽

Genome Wide ◽

Non Coding Rnas

It is of significance to mine the structural genes related to the biosynthetic pathway of fatty acid (FA) and cellulose as well as explore the regulatory mechanism of alternative splicing (AS), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the biosynthesis of cannabinoids, FA and cellulose, which would enhance the knowledge of gene expression and regulation at post-transcriptional level in Cannabis sativa L. In this study, transcriptome, small RNA and degradome libraries of hemp ‘Yunma No.1’ were established, and comprehensive analysis was performed. As a result, a total of 154, 32 and 331 transcripts encoding key enzymes involved in the biosynthesis of cannabinoids, FA and cellulose were predicted, respectively, among which AS occurred in 368 transcripts. Moreover, 183 conserved miRNAs, 380 C. sativa-specific miRNAs and 7783 lncRNAs were predicted. Among them, 70 miRNAs and 17 lncRNAs potentially targeted 13 and 17 transcripts, respectively, encoding key enzymes or transporters involved in the biosynthesis of cannabinoids, cellulose or FA. Finally, the crosstalk between AS and miRNAs or lncRNAs involved in cannabinoids and cellulose was also predicted. In summary, all these results provided insights into the complicated network of gene expression and regulation in C. sativa.

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Draft Whole-Genome Sequence of the Alkane-Synthesizing Polar Cyanobacterium Pseudanabaena biceps Strain O-153

Microbiology Resource Announcements ◽

10.1128/mra.00904-20 ◽

2020 ◽

Vol 9 (47) ◽

Author(s):

Bérangère Péquin ◽

Julien Tremblay ◽

Christine Maynard ◽

Jessica Wasserscheid ◽

Charles W. Greer

Keyword(s):

Genome Sequence ◽

Biosynthetic Pathway ◽

Whole Genome Sequence ◽

Whole Genome ◽

Content Type ◽

Key Enzymes ◽

Alkane Biosynthesis

ABSTRACT Alkane biosynthesis by polar cyanobacteria has not yet been reported. We present here the draft whole-genome sequence of an alkane-synthesizing polar cyanobacterium, Pseudanabaena biceps strain O-153. The genes coding for the two key enzymes involved in the alkane biosynthetic pathway were found contiguously in the genome.

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Overexpression ofAaWRKY1Leads to an Enhanced Content of Artemisinin inArtemisia annua

BioMed Research International ◽

10.1155/2016/7314971 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Weimin Jiang ◽

Xueqing Fu ◽

Qifang Pan ◽

Yueli Tang ◽

Qian Shen ◽

...

Keyword(s):

Transcription Factors ◽

Transgenic Plants ◽

Biosynthetic Pathway ◽

High Expression ◽

35S Promoter ◽

Key Enzymes ◽

Key Enzyme ◽

Effective Component ◽

Artemisinin Biosynthesis ◽

Insight Into

Artemisinin is an effective component of drugs against malaria. The regulation of artemisinin biosynthesis is at the forefront of artemisinin research. Previous studies showed that AaWRKY1 can regulate the expression ofADS, which is the first key enzyme in artemisinin biosynthetic pathway. In this study,AaWRKY1was cloned, and it activated ADSpro and CYPpro in tobacco using dual-LUC assay. To further study the function of AaWRKY1, pCAMBIA2300-AaWRKY1 construct under 35S promoter was generated. Transgenic plants containingAaWRKY1were obtained, and four independent lines with high expression ofAaWRKY1were analyzed. The expression ofADSandCYP, the key enzymes in artemisinin biosynthetic pathway, was dramatically increased inAaWRKY1-overexpressingA. annuaplants. Furthermore, the artemisinin yield increased significantly inAaWRKY1-overexpressingA. annuaplants. These results showed that AaWRKY1 increased the content of artemisinin by regulating the expression of bothADSandCYP. It provides a new insight into the mechanism of regulation on artemisinin biosynthesis via transcription factors in the future.

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New Sipanmycin Analogues Generated by Combinatorial Biosynthesis and Mutasynthesis Approaches Relying on the Substrate Flexibility of Key Enzymes in the Biosynthetic Pathway

Applied and Environmental Microbiology ◽

10.1128/aem.02453-19 ◽

2019 ◽

Vol 86 (3) ◽

Cited By ~ 2

Author(s):

Mónica G. Malmierca ◽

Ignacio Pérez-Victoria ◽

Jesús Martín ◽

Fernando Reyes ◽

Carmen Méndez ◽

...

Keyword(s):

Biosynthetic Pathway ◽

Polyketide Synthase ◽

Multidrug Resistant ◽

Chemotherapeutic Agents ◽

Combinatorial Biosynthesis ◽

Resistant Bacteria ◽

Cytotoxic Activities ◽

New Members ◽

Key Enzymes ◽

Enzymatic Machinery

ABSTRACT The appearance of new infectious diseases, the increase in multidrug-resistant bacteria, and the need for more effective chemotherapeutic agents have oriented the interests of researchers toward the search for metabolites with novel or improved bioactivities. Sipanmycins are disaccharyl glycosylated macrolactams that exert antibiotic and cytotoxic activities. By applying combinatorial biosynthesis and mutasynthesis approaches, we have generated eight new members of the sipanmycin family. The introduction of plasmids harboring genes responsible for the biosynthesis of several deoxysugars into sipanmycin-producing Streptomyces sp. strain CS149 led to the production of six derivatives with altered glycosylation patterns. After structural elucidation of these new metabolites, we conclude that some of these sugars are the result of the combination of the enzymatic machinery encoded by the introduced plasmids and the native enzymes of the d-sipanose biosynthetic pathway of the wild-type CS149 strain. In addition, two analogues of the parental compounds with a modified polyketide backbone were generated by a mutasynthesis approach, feeding cultures of a mutant strain defective in sipanmycin biosynthesis with 3-aminopentanoic acid. The generation of new sipanmycin analogues shown in this work relied on the substrate flexibility of key enzymes involved in sipanmycin biosynthesis, particularly the glycosyltransferase pair SipS9/SipS14 and enzymes SipL3, SipL1, SipL7, and SipL2, which are involved in the incorporation of the polyketide synthase starting unit. IMPORTANCE Combinatorial biosynthesis has proved its usefulness in generating derivatives of already known compounds with novel or improved pharmacological properties. Sipanmycins are a family of glycosylated macrolactams produced by Streptomyces sp. strain CS149, whose antiproliferative activity is dependent on the sugar moieties attached to the aglycone. In this work, we report the generation of several sipanmycin analogues with different deoxysugars, showing the high degree of flexibility exerted by the glycosyltransferase machinery with respect to the recognition of diverse nucleotide-activated sugars. In addition, modifications in the macrolactam ring were introduced by mutasynthesis approaches, indicating that the enzymes involved in incorporating the starter unit have a moderate ability to introduce different types of β-amino acids. In conclusion, we have proved the substrate flexibility of key enzymes involved in sipanmycin biosynthesis, especially the glycosyltransferases, which can be exploited in future experiments.

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