scholarly journals Amorpha-4,11-diene synthase: a key enzyme in artemisinin biosynthesis and engineering

aBIOTECH ◽  
2021 ◽  
Author(s):  
Jing-Quan Huang ◽  
Xin Fang
Keyword(s):  
Metabolic Engineering ◽  
Synthetic Biology ◽  
Biosynthetic Pathway ◽  
Catalytic Mechanism ◽  
Artemisia Annua ◽  
New Techniques ◽  
Key Enzyme ◽  
Substrate Promiscuity ◽  
Artemisinin Biosynthesis

AbstractAmorpha-4,11-diene synthase (ADS) catalyzes the first committed step in the artemisinin biosynthetic pathway, which is the first catalytic reaction enzymatically and genetically characterized in artemisinin biosynthesis. The advent of ADS in Artemisia annua is considered crucial for the emergence of the specialized artemisinin biosynthetic pathway in the species. Microbial production of amorpha-4,11-diene is a breakthrough in metabolic engineering and synthetic biology. Recently, numerous new techniques have been used in ADS engineering; for example, assessing the substrate promiscuity of ADS to chemoenzymatically produce artemisinin. In this review, we discuss the discovery and catalytic mechanism of ADS, its application in metabolic engineering and synthetic biology, as well as the role of sesquiterpene synthases in the evolutionary origin of artemisinin.

scholarly journals Role of Ethylene in the Biosynthetic Pathway of Related-aroma Volatiles Derived from Fatty Acids in Oriental Sweet Melon

2016 ◽  
Vol 141 (4) ◽  
pp. 327-338 ◽  
Author(s):  
Yan Li ◽  
Hongyan Qi ◽  
Yazhong Jin ◽  
Xiaobin Tian ◽  
Linlin Sui ◽  
...  
Keyword(s):  
Volatile Compounds ◽  
Biosynthetic Pathway ◽  
Expression Patterns ◽  
Gene Families ◽  
Hydroperoxide Lyase ◽  
Straight Chain ◽  
Alcohol Acetyltransferase ◽  
Key Enzyme ◽  
Aroma Precursors

The catabolism of fatty acid (FA) is regarded as a key pathway of aroma volatile compounds in oriental sweet melon (Cucumis melo var. makuwa). In our research, two cultivars of oriental sweet melon, Caihong7 and Tianbao, were employed to illuminate which step of the biosynthetic pathway of aroma compounds could be regulated by ethylene (ETH). The role of ETH in determining the profiles of straight-chain aroma volatile compounds, levels of FA as aroma precursors, activities of aroma-related enzymes derived from FA pathway, and expression patterns of key enzymes were investigated. Overall, exogenous application of ETH increased the production rates of endogenous ETH and levels of FA. Compared with control, the level of straight-chain esters, especially the acetate, hexanoate, and hexyl esters, was significantly increased by ETH, whereas the content of alcohol and aldehyde reduced. In addition, the metabolism of free FA included linoleic acid (LA), linolenic acid (LeA), and oleic acid (OA) appeared to be ETH-dependent. The activities of lipoxygenase (LOX), alcohol dehydrogenase (ADH), and alcohol acetyltransferase (AAT) as well as the expression patterns of Cm-ADH1, Cm-ADH2, Cm-AAT1, and Cm-AAT4 were positively regulated by ETH. In contrast, hydroperoxide lyase (HPL) and Cm-AAT2 and Cm-AAT3 seemed to be independent of ETH modulation. These results suggested that the dissimilation of FA included LA, LeA, and OA into the acetate, hexanoate, and hexyl esters mainly through ETH regulating the LOX pathway by enhancing the expression of particular members of aroma-related key enzyme gene families as well as the activities of dehydrogenation and esterification.

Metabolic engineering of artemisinin biosynthesis in Artemisia annua L.

2010 ◽  
Vol 30 (5) ◽  
pp. 689-694 ◽  
Author(s):  
Benye Liu ◽  
Hong Wang ◽  
Zhigao Du ◽  
Guofeng Li ◽  
Hechun Ye
Keyword(s):  
Metabolic Engineering ◽  
Artemisia Annua ◽  
Artemisia Annua L ◽  
Artemisinin Biosynthesis

COX-2: A Molecular Target for Colorectal Cancer Prevention

2005 ◽  
Vol 23 (12) ◽  
pp. 2840-2855 ◽  
Author(s):  
Joanne R. Brown ◽  
Raymond N. DuBois
Keyword(s):  
Biosynthetic Pathway ◽  
Experimental Studies ◽  
Protective Effects ◽  
Randomized Controlled Studies ◽  
Key Enzyme ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Colorectal Cancer Prevention ◽  
Cox 2 Inhibitors

Cyclooxygenase (COX), a key enzyme in the prostanoid biosynthetic pathway, has received considerable attention due to its role in human cancers. Observational and randomized controlled studies in many different population cohorts and settings have demonstrated protective effects of nonsteroidal anti-inflammatory drugs (NSAIDs; the inhibitors of COX activity) for colorectal cancers (CRCs). COX-2, the inducible isoform of cyclooxygenase, is overexpressed in early and advanced CRC tissues, which portends a poor prognosis. Experimental studies have thus identified important mechanisms and pathways by which COX-2 plays an important role in carcinogenesis. Selective COX-2 inhibitors have been approved for use as adjunctive therapy for patients with familial polyposis. The role of COX-2 inhibitors is currently being evaluated for use in wider populations.

Artemisinin biosynthesis in Artemisia annua and metabolic engineering: questions, challenges, and perspectives

2016 ◽  
Vol 15 (6) ◽  
pp. 1093-1114 ◽  
Author(s):  
De-Yu Xie ◽  
Dong-Ming Ma ◽  
Rika Judd ◽  
Ashley Loray Jones
Keyword(s):  
Metabolic Engineering ◽  
Artemisia Annua ◽  
Artemisinin Biosynthesis

scholarly journals Overexpression ofAaWRKY1Leads to an Enhanced Content of Artemisinin inArtemisia annua

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
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.

Molecular Cloning, Expression, and Characterization of Amorpha-4,11-diene Synthase, a Key Enzyme of Artemisinin Biosynthesis in Artemisia annua L.

2000 ◽  
Vol 381 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Per Mercke ◽  
Marie Bengtsson ◽  
Harro J. Bouwmeester ◽  
Maarten A. Posthumus ◽  
Peter E. Brodelius
Keyword(s):  
Molecular Cloning ◽  
Artemisia Annua ◽  
Artemisia Annua L ◽  
Key Enzyme ◽  
Artemisinin Biosynthesis

scholarly journals The Azotobacter vinelandii Response Regulator AlgR Is Essential for Cyst Formation

1999 ◽  
Vol 181 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Cinthia Núñez ◽  
Soledad Moreno ◽  
Gloria Soberón-Chávez ◽  
Guadalupe Espín
Keyword(s):  
Electron Microscopy ◽  
Pseudomonas Aeruginosa ◽  
Biosynthetic Pathway ◽  
Azotobacter Vinelandii ◽  
Response Regulator ◽  
Cyst Formation ◽  
Sensor Kinase ◽  
Alginate Production ◽  
Key Enzyme

ABSTRACT Azotobacter vinelandii produces the exopolysaccharide alginate, which is essential for the encystment process. InPseudomonas aeruginosa, as well as in A. vinelandii, the ςE factor encoded byalgU is required for transcription of algD, which encodes a key enzyme of the alginate biosynthetic pathway. TheP. aeruginosa response regulator AlgR activates transcription of algD. fimS, located upstreamalgR, is proposed to encode the AlgR cognate sensor kinase. We have cloned and characterized the A. vinelandii algRgene; the deduced amino acid sequence of the protein encoded by this gene shows 79% identity with its P. aeruginosa homolog. Sequence analysis around the algR gene revealed the absence of a fimS homolog. Inactivation of A. vinelandii algR diminished alginate production by 50%, but did not affectalgD transcription, and completely impaired the capacity to form mature cysts. Electron microscopy of the cyst structures formed by the algR mutant revealed that the encystment process is blocked at the step of exine formation. The transcriptional regulation of the A. vinelandii algR gene and the role of AlgR in alginate production differ significantly from those of its P. aeruginosa counterparts. These differences could be due to the fact that in A. vinelandii, alginate plays a role in encystment, a function not found in P. aeruginosa.

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