Berberine bridge enzyme-like oxidase-catalysed double bond isomerization acts as the pathway switch in cytochalasin synthesis

AbstractCytochalasans (CYTs), as well as their polycyclic (pcCYTs) and polymerized (meCYTs) derivatives, constitute one of the largest families of fungal polyketide-nonribosomal peptide (PK-NRP) hybrid natural products. However, the mechanism of chemical conversion from mono-CYTs (moCYTs) to both pcCYTs and meCYTs remains unknown. Here, we show the first successful example of the reconstitution of the CYT core backbone as well as the whole pathway in a heterologous host. Importantly, we also describe the berberine bridge enzyme (BBE)-like oxidase AspoA, which uses Glu538 as a general acid biocatalyst to catalyse an unusual protonation-driven double bond isomerization reaction and acts as a switch to alter the native (for moCYTs) and nonenzymatic (for pcCYTs and meCYTs) pathways to synthesize aspochalasin family compounds. Our results present an unprecedented function of BBE-like enzymes and highly suggest that the isolated pcCYTs and meCYTs are most likely artificially derived products.

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1-Hexene Double Bond Isomerization Reaction Over SO 4 = Promoted NiO, Al2O3 and ZrO2 Acid Catalysts

Catalysis Letters ◽

10.1007/s10562-008-9714-z ◽

2008 ◽

Vol 128 (3-4) ◽

pp. 290-296 ◽

Cited By ~ 5

Author(s):

M. Pérez-Luna ◽

A. Cosultchi ◽

J. A. Toledo-Antonio ◽

L. Díaz-Garcia

Keyword(s):

Double Bond ◽

Isomerization Reaction ◽

Acid Catalysts ◽

Double Bond Isomerization

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Biosynthesis of Yersiniabactin, a Complex Polyketide-Nonribosomal Peptide, Using Escherichia coli as a Heterologous Host

Applied and Environmental Microbiology ◽

10.1128/aem.69.11.6698-6702.2003 ◽

2003 ◽

Vol 69 (11) ◽

pp. 6698-6702 ◽

Cited By ~ 80

Author(s):

Blaine A. Pfeifer ◽

Clay C. C. Wang ◽

Christopher T. Walsh ◽

Chaitan Khosla

Keyword(s):

Escherichia Coli ◽

Natural Products ◽

High Cell Density ◽

High Cell ◽

Biochemical Pathway ◽

Heterologous Host ◽

Nonribosomal Peptide ◽

E Coli ◽

Future Production ◽

Medicinal Value

ABSTRACT The medicinal value associated with complex polyketide and nonribosomal peptide natural products has prompted biosynthetic schemes dependent upon heterologous microbial hosts. Here we report the successful biosynthesis of yersiniabactin (Ybt), a model polyketide-nonribosomal peptide hybrid natural product, using Escherichia coli as a heterologous host. After introducing the biochemical pathway for Ybt into E. coli, biosynthesis was initially monitored qualitatively by mass spectrometry. Next, production of Ybt was quantified in a high-cell-density fermentation environment with titers reaching 67 ± 21 (mean ± standard deviation) mg/liter and a volumetric productivity of 1.1 ± 0.3 mg/liter-h. This success has implications for basic and applied studies on Ybt biosynthesis and also, more generally, for future production of polyketide, nonribosomal peptide, and mixed polyketide-nonribosomal peptide natural products using E. coli.

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Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.11.101 ◽

2015 ◽

Vol 11 ◽

pp. 897-905 ◽

Cited By ~ 16

Author(s):

Sultan Taskaya ◽

Nurettin Menges ◽

Metin Balci

Keyword(s):

Natural Products ◽

Double Bond ◽

Marine Natural Products ◽

Cascade Reactions ◽

Cyclization Reaction ◽

Cyclization Reactions ◽

Double Bond Isomerization

Various N-propargylpyrrole and indolecarboxylic acids were efficiently converted into 3,4-dihydropyrrolo- and indolo-oxazin-1-one derivatives by a gold(III)-catalyzed cyclization reaction. Some of the products underwent TFA-catalyzed double bond isomerization and some did not. Cyclization reactions in the presence of alcohol catalyzed by Au(I) resulted in the formation of hemiacetals after cascade reactions.

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Combinatorial Synthesis of Novel 9R-Acyloxyquinine Derivatives as Insecticidal Agents

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200120112714 ◽

2020 ◽

Vol 23 (2) ◽

pp. 111-118

Author(s):

Zhiping Che ◽

Jinming Yang ◽

Di Sun ◽

Yuee Tian ◽

Shengming Liu ◽

...

Keyword(s):

Natural Products ◽

Double Bond ◽

Insecticidal Activity ◽

Structural Modification ◽

Combinatorial Synthesis ◽

Hydroxyl Group ◽

Botanical Insecticide ◽

Mythimna Separata ◽

Lead Compounds

Background: It is one of the effective ways for pesticide innovation to develop new insecticides from natural products as lead compounds. Quinine, the main alkaloid in the bark of cinchona tree as well as in plants in the same genus, is recognized as a safe and potent botanical insecticide to many insects. The structural modification of quinine into 9R-acyloxyquinine derivatives is a potential approach for the development of novel insecticides, which showed more toxicity than quinine. However, there are no reports on the insecticidal activity of 9Racyloxyquinine derivatives to control Mythimna separata. Methods: Endeavor to discover biorational natural products-based insecticides, 20 novel 9Racyloxyquinine derivatives were prepared and assessed for their insecticidal activity against M. separata in vivo by the leaf-dipping method at 1 mg/mL. Results: Among all the compounds, especially derivatives 5i, 5k and 5t exhibited the best insecticidal activity with final mortality rates of 50.0%, 57.1%, and 53.6%, respectively. Conclusion: Overall, a free 9-hydroxyl group is not a prerequisite for insecticidal activity and C9- substitution is well tolerated; modification of out-ring double-bond is acceptable, and hydrogenation of double-bond enhances insecticidal activity; Quinine ring is essential and open of it is not acceptable. These preliminary results will pave the way for further modification of quinine in the development of potential new insecticides.

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Mechanisms of Double-Bond Isomerization Reactions of n-Butene on Different Lewis Acids

ACS Catalysis ◽

10.1021/acscatal.1c02846 ◽

2021 ◽

pp. 11293-11304

Author(s):

Fengjiao Yi ◽

Peng He ◽

Huimin Chen ◽

Yurong He ◽

Zhichao Tao ◽

...

Keyword(s):

Double Bond ◽

Lewis Acids ◽

Double Bond Isomerization

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Double bond isomerization of ethyl linoleate and vegetable oils to conjugated derivatives over an LDH supported ruthenium catalyst

RSC Advances ◽

10.1039/c5ra04822b ◽

2015 ◽

Vol 5 (45) ◽

pp. 36075-36082 ◽

Cited By ~ 2

Author(s):

Sivashunmugam Sankaranarayanan ◽

Gobi Selvam ◽

Kannan Srinivasan

Keyword(s):

Double Bond ◽

Vegetable Oils ◽

Ethyl Linoleate ◽

Ruthenium Catalyst ◽

Reaction Conditions ◽

Double Bond Isomerization

Isomerization of ethyl linoleate and vegetable oils to conjugated derivatives is achieved over an MgAl-LDH supported ruthenium catalyst under mild reaction conditions.

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9, 13-dicis-Rhodopsin and its one-photon-one-double-bond isomerization

Biochemistry ◽

10.1021/bi00417a044 ◽

1988 ◽

Vol 27 (17) ◽

pp. 6495-6499 ◽

Cited By ~ 26

Author(s):

Yoshinori Shichida ◽

Katsuki Nakamura ◽

Toru Yoshizawa ◽

Achla Trehan ◽

Marlene Denny ◽

...

Keyword(s):

Double Bond ◽

Double Bond Isomerization

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Total Biosynthesis and Diverse Applications of the Nonribosomal Peptide-Polyketide Siderophore Yersiniabactin

Applied and Environmental Microbiology ◽

10.1128/aem.01373-15 ◽

2015 ◽

Vol 81 (16) ◽

pp. 5290-5298 ◽

Cited By ~ 21

Author(s):

Mahmoud Kamal Ahmadi ◽

Samar Fawaz ◽

Charles H. Jones ◽

Guojian Zhang ◽

Blaine A. Pfeifer

Keyword(s):

Polyketide Synthase ◽

Parallel Applications ◽

Total Removal ◽

Heterologous Host ◽

Nonribosomal Peptide ◽

Content Type ◽

Metal Chelating ◽

Removal Capacity ◽

Peptide Synthetase ◽

Host Infection

ABSTRACTYersiniabactin (Ybt) is a mixed nonribosomal peptide-polyketide natural product natively produced by the pathogenYersinia pestis. The compound enables iron scavenging capabilities upon host infection and is biosynthesized by a nonribosomal peptide synthetase featuring a polyketide synthase module. This pathway has been engineered for expression and biosynthesis usingEscherichia colias a heterologous host. In the current work, the biosynthetic process for Ybt formation was improved through the incorporation of a dedicated step to eliminate the need for exogenous salicylate provision. When this improvement was made, the compound was tested in parallel applications that highlight the metal-chelating nature of the compound. In the first application, Ybt was assessed as a rust remover, demonstrating a capacity of ∼40% compared to a commercial removal agent and ∼20% relative to total removal capacity. The second application tested Ybt in removing copper from a variety of nonbiological and biological solution mixtures. Success across a variety of media indicates potential utility in diverse scenarios that include environmental and biomedical settings.

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