Production of anticancer polyenes through precursor-directed biosynthesis

Clark, Benjamin R.; OʼConnor, Stephen J; Fox, Deirdre; Leroy, Jacques; Murphy, Cormac D.

doi:10.1039/c1ob05667k

Cited by 25 publications

(15 citation statements)

References 22 publications

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“…The known compounds (AE)-4 -15, 17 -20, and 22 were identified as (S)-5-methoxy-D 3 -pyrrolin-2-one ((+)-4), [24] (R)-5-methoxy-D 3 -pyrrolin-2-one ((À)-4) [24] (the (5R)-and (5S)-configurations were determined by comparing the optical rotations with those of (AE)-2), (Z)-N-(3-(2,5-dioxoimidazolidin-4-ylidene)propyl)-1H-pyrrole-2-carboxamide (5), [25] b-alanine methyl esters (6), [26] N-(pyrrole-2-carbonyl)glycine methyl esters (7), [27] N-(2-hydroxyethyl)-1H-pyrrole-2-carboxamide (8), [28] N-formylpyrrole-2-carboxamide (9), [29] 1H-pyrrole-2-carboxamide (10), [29] 4-bromo-1H-pyrrole-2-carboxamide (11), [30] 5-bromo-1H-pyrrole-2-carboxamide (12), [30] 1H-pyrrole-2-carboxylic acid (13) [31] , 4-bromopyrrole-2-carboxylic acid (14), [32] 5-bromopyrrole-2-carboxylic acid (15), [32] agelasine B (17), [8] agelasine J (18), [15] nemoechine G (19), [10] 2-oxoagelasine B (20), [33] and (À)-agelasidine C (22), [34] by comparing their spectra data with those reported earlier.…”

Section: Structure Elucidationmentioning

confidence: 99%

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai

Chu

Tang

Qin

et al. 2017

Chemistry & Biodiversity

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Two pairs of new non-brominated racematic pyrrole derivatives, (±)-nakamurine D (1) and (±)-nakamurine E (2), two new diterpene alkaloids, isoagelasine C (16) and isoagelasidine B (21), together with 13 known pyrrole derivatives ((±)-3 - 15), five known diterpene alkaloids (17 - 20, 22) were isolated from the South China Sea sponge Agelas nakamurai. The racemic mixtures, compounds 1 - 4, were resolved into four pairs of enantiomers, (+)-1 and (-)-1, (+)-2 and (-)-2, (+)-3 and (-)-3, and (+)-4 and (-)-4, by chiral HPLC. The structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, quantum chemical calculations, quantitative measurements of molar rotations, application of van't Hoff's principle of optical superposition, and comparison with the literature data. The NMR and MS data of compound 3 are reported for the first time, as the structure was listed in SciFinder Scholar with no associated reference. These non-brominated pyrrole derivatives were found in this species for the first time. Compound 18 showed valuable cytotoxicities against HL-60, K562, and HCT-116 cell lines with IC values of 12.4, 16.0, and 19.8 μm, respectively. Compounds 16 - 19, 21, and 22 showed potent antifungal activities against Candida albicans with MIC values ranging from 0.59 to 4.69 μg/ml. Compounds 16 - 19 exhibited moderate antibacterial activities against Proteusbacillus vulgaris (MIC values ranging from 9.38 to 18.75 μg/ml).

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Section: Structure Elucidationmentioning

confidence: 99%

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai

Chu

Tang

Qin

et al. 2017

Chemistry & Biodiversity

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“…Next, we investigated whether 1 can form different vibralactones through divergent pathways, based on the traditional platform of precursor‐directed biosynthesis . Since an allyl C 3 mark is extremely rare in natural products from higher fungi, compound 1 a , an analogue of 1 that contains an allyl rather than a prenyl moiety, was synthesized and fed (2 m m ) to a culture (500 mL) of B. vibrans on day 12 after inoculation.…”

Section: Figurementioning

confidence: 99%

A Monooxygenase from Boreostereum vibrans Catalyzes Oxidative Decarboxylation in a Divergent Vibralactone Biosynthesis Pathway

Yang

Zhou

et al. 2016

Angewandte Chemie

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The oxidative decarboxylation of prenyl 4-hydroxybenzoate to prenylhydroquinone has been frequently proposed for the biosynthesis of prenylated (hydro)quinone derivates (sometimes meroterpenoids), yet no corresponding genes or enzymes have so far been reported. AF AD-binding monooxygenase (VibMO1) was identified that converts prenyl 4hydroxybenzoate into prenylhydroquinone and is likely involved in the biosynthesis of vibralactones and other meroterpenoids in the basidiomycete Boreostereum vibrans. Feeding of 3-allyl-4-hydroxybenzylalcohol, an analogue of the vibralactone pathway intermediate 3-prenyl-4-hydroxybenzylalcohol, generated 20 analogues with different scaffolds.This demonstrated divergent pathwayst os keletally distinct compounds initiating from as ingle precursor,t hus providing the first insight into anovel biosynthetic pathway for 3-substituted g-butyrolactones from ashikimate origin.

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“…The 3-chloro- and 3-bromo-isorumbrin were more potent than rumbrin, and 3-bromo-isorumbrin exhibited improved anticancer activity. 22 To yield diazepinomicin analogs with modified ring-A, Ratnayake et al 23 fed potential ring-A precursors such as fluorinated tryptophans, halogenated anthranilates, and various substituted indoles to the marine actinomycete culture ( Micromonospora sp. strain DPJ15).…”

Section: Precursor-directed Combinatorial Biosynthesismentioning

confidence: 99%

Recent advances in combinatorial biosynthesis for drug discovery

Sun

Liu

Zhao

et al. 2015

DDDT

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Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel “unnatural” natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1) precursor-directed biosynthesis; 2) enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3) pathway-level recombination. Recent examples of combinatorial biosynthesis employing these strategies will also be highlighted in this review.

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Production of anticancer polyenes through precursor-directed biosynthesis

Cited by 25 publications

References 22 publications

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai

A Monooxygenase from Boreostereum vibrans Catalyzes Oxidative Decarboxylation in a Divergent Vibralactone Biosynthesis Pathway

Recent advances in combinatorial biosynthesis for drug discovery

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Production of anticancer polyenes through precursor-directed biosynthesis

Cited by 25 publications

References 22 publications

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai

A Monooxygenase from Boreostereum vibrans Catalyzes Oxidative Decarboxylation in a Divergent Vibralactone Biosynthesis Pathway

Recent advances in combinatorial biosynthesis for&nbsp;drug discovery

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Recent advances in combinatorial biosynthesis for drug discovery