Total synthesis of xiamenmycin C and all of its stereoisomers: stereochemical revision

Yao, Yangyang; Liu, Xiaoyu; Li, Xiaoyü; Yang, Hai; Li, Li; Jiao, Xiaozhen; Xie, Ping

doi:10.1080/10286020.2016.1188808

Cited by 4 publications

(4 citation statements)

References 23 publications

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“…Nonetheless, great efforts have been made to obtain this promising pharmacophore. The chemical synthesis processes of 3-chromanols have been intensively investigated, ,,− including Au-catalyzed intramolecular cycloalkylation, FeBr 3 /3AgOTf-mediated cyclization of aryl glycidyl ether, and VO(acac) 2 /TBHP catalyzed oxidative cyclization . Biologists tried to produce bioactive 3-chromanol-containing derivatives via Mycobacterium biotransformation and engineered the metabolic pathway to improve the production of pyranocoumarins in native plant hosts. , An environmentally friendly, renewable, and sustainable strategy to produce this widely spread bioactive skeleton is still unavailable.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Pyran Formation Involved in Xiamenmycin Biosynthesis

Zhou

et al. 2019

ACS Catal.

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The pyran ring is a very common structural unit of many natural, bioactive molecules that are widely found in plants, bacteria, and fungi. However, the enzymatic processes by which many of these pyran-containing molecules are formed are unclear. Herein, we report the construction of the pyran ring catalyzed by the cooperation of a flavin-dependent monooxygenase, XimD, and a SnoaL-like cyclase, XimE, in the biosynthesis of xiamenmycins. XimD catalyzes the formation of an epoxide intermediate that spontaneously transforms to furan and pyran products (43:1) in vitro. XimE then catalyzes the formation of the pyran ring in a 6-endo configuration from the epoxide to yield a benzopyran, xiamenmycin B. Further, we obtained the crystallographic structure of XimE, with and without product, which suggests a synergistic mechanism in which a group of four residues (Y46–Y90–H102–E136) acts cooperatively as the general acid and base. Subsequent structure-based analysis of possible viable substrates indicates that both XimD and XimE exhibit high promiscuity in their catalysis. Overall, this study reveals the mechanism of pyran ring formation in xiamenmycin biosynthesis and demonstrates the potential application of XimD and XimE in the biosynthesis of other benzoheterocycle scaffolds, including furano- and pyranocoumarins.

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Section: Introductionmentioning

confidence: 99%

Enzymatic Pyran Formation Involved in Xiamenmycin Biosynthesis

Zhou

et al. 2019

ACS Catal.

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“…Dereplicated compounds, as mentioned in Figure 2 , are characterized by being of a different chemical nature. The dereplicated compounds include lorneamide A ( 1 ) [ 15 ], xiamenmycin C ( 2 ) [ 16 ], linieodolide A ( 3 ) [ 17 ], rhopaloic acid F ( 4 ) [ 18 ], crambine C2 ( 5 ) [ 19 ], norcrambescin C1 ( 6 ) [ 20 ], nebrosteroid C ( 7 ) [ 21 ], iriomoteolide 1b ( 8 ) [ 22 ], cytoglobosin G ( 9 ) [ 23 ], hippospongide A ( 10 ) [ 24 ], and trunculin A ( 11 ) [ 25 ] ( Table S2 ).…”

Section: Resultsmentioning

confidence: 99%

Network Pharmacological Analysis of the Red Sea Sponge Hyrtios erectus Extract to Reveal Anticancer Efficacy of Corresponding Loaded Niosomes

Abou-Taleb¹,

Sayed

Refaat

et al. 2022

Marine Drugs

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In this study, the LC-HRMS-assisted chemical profiling of Hyrtios erectus sponge led to the annotation of eleven major compounds (1–11). H. erectus-derived crude extract (HE) was tested in vitro for its antiproliferative activity against three human cancer cell lines, Hep-G2 (human liver cancer cell line), MCF-7 (breast cancer cell line), and Caco-2 (colon cancer cell line), before and after encapsulation within niosomes. Hyrtios erectus extract showed moderate in vitro antiproliferative activities towards the studied cell lines with IC50 values 18.5 ± 0.08, 15.2 ± 0.11, and 13.4 ± 0.12, respectively. The formulated extract-containing niosomes (size 142.3 ± 10.3 nm, PDI 0.279, and zeta potential 22.8 ± 1.6) increased the in vitro antiproliferative activity of the entrapped extract significantly (IC50 8.5 ± 0.04, 4.1 ± 0.07, and 3.4 ± 0.05, respectively). A subsequent computational chemical study was performed to build a sponge–metabolite–targets–cancer diseases network, by focusing on targets that possess anticancer activity toward the three cancer types: breast, colon, and liver. Pubchem, BindingDB, and DisGenet databases were used to build the network. Shinygo and KEGG databases in addition to FunRich software were used for gene ontology and functional analysis. The computational analysis linked the metabolites to 200 genes among which 147 genes related to cancer and only 64 genes are intersected in the three cancer types. The study proved that the co-occurrence of compounds 1, 2, 3, 7, 8, and 10 are the most probable compounds possessing cytotoxic activity due to large number of connections to the intersected cytotoxic genes with edges range from 9-14. The targets possess the anticancer effect through Pathways in cancer, Endocrine resistance and Proteoglycans in cancer as mentioned by KEGG and ShinyGo 7.1 databases. This study introduces niosomes as a promising strategy to promote the cytotoxic potential of H. erectus extract.

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“…In this study, we further exploited the GBA synthesis platform by introducing the modifying enzymes XimD and XimE to convert GBA to the benzopyran compound, xiamenmycin B. As the final step in the formation of the benzopyran xiamenmycin B, the epoxidation and cyclization of GBA with tert -butyl hydroperoxide ( t -BuOOH)/vanadyl acetylacetonate (VO(acac) 2 )/TFA can yield (2 R, 3 S ) xiamenmycin B in 77% ee. , However, because of the S N 2 mechanism, the product of xiamenmycin B is enantiomorphous, which led to (2 R , 3 S ) and its enantioisomer (2 S , 3 R ) . Furthermore, other modifications, such as the cyclization of prenylated aromatic compounds, also play an important role in the biosynthesis of meroterpenoids .…”

Section: Discussionmentioning

confidence: 99%

“…K M values for DMAPP, GPP, and FPP were separately measured at varying concentrations (5,10,20,30,40,50,60,70,80,90,100,150,200,250,300,350, and 400 μM) in the presence of 50 mM Tris-HCl buffer (pH 7.5), 5 mM 4-HBA, 5 mM MgCl 2 , and 150 μg total protein in the final volume of 60 μL. Reactions were performed at 30 °C for 1 h for GPP and 1.5 h for DMAPP and FPP.…”

Section: ■ Methodsmentioning

confidence: 99%

Combinatory Biosynthesis of Prenylated 4-Hydroxybenzoate Derivatives by Overexpression of the Substrate-Promiscuous Prenyltransferase XimB in Engineered E. coli

He¹,

Bu²,

Zhou³

et al. 2018

ACS Synth. Biol.

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Prenylated aromatic compounds are important intermediates in the biosynthesis of bioactive molecules such as 3-chromanols from plants, ubiquinones from prokaryotes and meroterpenoids from sponges. Biosynthesis of prenylated aromatic compounds using prokaryotic microorganisms has attracted increasing attention in the field of synthetic biology. In this study, we demonstrated that the production of 3-geranyl-4-hydroxybenzoic acid (GBA) and a variety of GBA analogues was feasible in a metabolically engineered E. coli by using XimB, a special prenyltransferase involved in the biosynthesis of xiamenmycin A in Streptomyces xiamenensis 318. XimB exhibits broad substrate specificity and can catalyze the transfer reaction of prenyl moieties with different carbon chain lengths to both the natural substrate 4-hydroxybenzoate (4-HBA) and to different substituted 4-HBA derivatives at C-2 and C-3. Feeding 4-HBA to an engineered E. coli equipped with a hybrid mevalonate pathway increased the production of GBA up to 94.30 mg/L. Considerable amounts of other GBA derivatives, compounds 4, 5, 6, 7, and 9, can be achieved by feeding precursors. The plug-and-play design for inserting C, C, and C prenyl diphosphate synthetases under the control of the T7 promoter resulted in targeted production of 3-dimethylallyl, 3-farnesyl-, and 3-geranylgeranyl-4-hydroxybenzoic acid, respectively. Furthermore, the valuable benzopyran xiamenmycin B was successfully produced in E. coli R7-MVA by coexpression of a complete biosynthetic gene cluster, which contains ximBDE.

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Total synthesis of xiamenmycin C and all of its stereoisomers: stereochemical revision

Abstract: Xiamenmycin C, a potent anti-fibrotic natural product, and all of its stereoisomers have been synthesized and their structures were fully characterized. Based on this study, the originally proposed structure of xiamenmycin C has been accordingly revised to be 2R,3S.

Cited by 4 publications

References 23 publications

Enzymatic Pyran Formation Involved in Xiamenmycin Biosynthesis

Enzymatic Pyran Formation Involved in Xiamenmycin Biosynthesis

Network Pharmacological Analysis of the Red Sea Sponge Hyrtios erectus Extract to Reveal Anticancer Efficacy of Corresponding Loaded Niosomes

Combinatory Biosynthesis of Prenylated 4-Hydroxybenzoate Derivatives by Overexpression of the Substrate-Promiscuous Prenyltransferase XimB in Engineered E. coli

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