459. The chemistry of bacteria. Part VIII. The synthesis of violacein and related compounds

Ballantine, James A.; Beer, R. J. S.; Crutchley, D. J.; Dodd, G. M.; Palmer, David R. J.

doi:10.1039/jr9600002292

Cited by 27 publications

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“…1) is a purple pigment that gives tropical bacterium Chromobacterium violaceum its characteristic coloring (1)(2)(3)(4)(5). Violacein 5 has potential medical applications as an antibacterial (6 -8), anti-tryptanocidal (8 -10), anti-ulcerogenic (11), and anti-cancer drug (8,(12)(13)(14)(15)(16)(17).…”

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The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins

Ryan

Balibar

Turo

et al. 2008

Journal of Biological Chemistry

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VioE, an unusual enzyme with no characterized homologues, plays a key role in the biosynthesis of violacein, a purple pigment with antibacterial and cytotoxic properties. Without bound cofactors or metals, VioE, from the bacterium Chromobacterium violaceum, mediates a 1,2 shift of an indole ring and oxidative chemistry to generate prodeoxyviolacein, a precursor to violacein. Our 1.21 Å resolution structure of VioE shows that the enzyme shares a core fold previously described for lipoprotein transporter proteins LolA and LolB. For both LolB and VioE, a bound polyethylene glycol molecule suggests the location of the binding and/or active site of the protein. Mutations of residues near the bound polyethylene glycol molecule in VioE have identified the active site and five residues important for binding or catalysis. This structural and mutagenesis study suggests that VioE acts as a catalytic chaperone, using a fold previously associated with lipoprotein transporters to catalyze the production of its prodeoxyviolacein product.Violacein 5 (Fig. 1) is a purple pigment that gives tropical bacterium Chromobacterium violaceum its characteristic coloring (1-5). Violacein 5 has potential medical applications as an antibacterial (6 -8), anti-tryptanocidal (8 -10), anti-ulcerogenic (11), and anti-cancer drug (8,(12)(13)(14)(15)(16)(17). The molecule, made of L-tryptophan and molecular oxygen (18 -21), was originally thought to be synthesized by the action of just four enzymes VioABCD (22, 23), but an additional open reading frame (24), also in the operon, was shown to encode the enzyme VioE (25, 26). A 22-kDa protein with few homologues based on sequence analysis, VioE is required for formation of prodeoxyviolacein 3, a precursor to violacein 5 (25-27). Without the presence of VioE, a shunt product, chromopyrrolic acid 4, is produced, rather than 3 (25-27). VioE is therefore required for the 1,2 shift of the indole ring and subsequent chemistry that gives violacein 5 its distinctive architecture. Surprisingly, despite carrying out this chemistry, VioE lacks any bound cofactors or metal ions (26).Using genetic and biochemical analysis, an enzymatic pathway for violacein 5 production has been determined ( Fig. 1), and intermediates have been identified (26), with the major exception that the substrate of VioE (product of VioB) is still unknown. It has, however, been established that the product of VioB is the substrate for VioE; when VioA and VioB are incubated in a reaction mixture with the VioA substrate L-tryptophan for 10 min, passed through a 10-kDa filter (removing VioA and VioB), and then incubated with VioE, prodeoxyviolacein 3 is produced (26). By contrast, in the absence of VioE, no prodeoxyviolacein 3 is made (26). This result reveals three things: first, the VioB product is a small molecule that can pass through a 10-kDa filter; second, no interaction between VioB and VioE is necessary for product formation; and third, VioE is a catalyst. The small molecule passed through the filter (the product of VioB and substra...

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confidence: 99%

The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins

Ryan

Balibar

Turo

et al. 2008

Journal of Biological Chemistry

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“…[19] Biosynthetic studies concerning violacein (15) and deoxyviolacein (16) have identified related 3-alkenyl-oxindoles as possible intermediates. [20] Indirubin (18) was first isolated from human blood plasma, urine and haemofiltrate of uraemic patients in 1986, [21] while its isomer isoindirubin (19) was isolated together with isoindigo (20) from the leaves of woad (Isatis tinctoria) in 2001. [22] Although a comprehensive listing will not be provided here, it should be noted that a number of polycyclic compounds are known which contain the 3-alkenyl-oxindole moiety.…”

Section: Introductionmentioning

confidence: 99%

“…pigment, violacein (15) was first isolated in 1934 [15,16] from the Amazonian bacteria Chromobacterium violaceum and has been reported to possess multiple biological activities, including in vitro antitumour effects. [17] The parent compound deoxyviolacein (16) was isolated from the same source in 1958 [18] and pseudodeoxyviolacein (17) was isolated from Chromobacterium violaceum in 1994. [19] Biosynthetic studies concerning violacein (15) and deoxyviolacein (16) have identified related 3-alkenyl-oxindoles as possible intermediates.…”

Section: Introductionmentioning

confidence: 99%

3‐Alkenyl‐oxindoles: Natural Products, Pharmaceuticals, and Recent Synthetic Advances in Tandem/Telescoped Approaches

2010

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The structures and biological activities of naturally occurring 3‐alkenyl‐oxindoles are reviewed. Important man‐made3‐alkenyl‐oxindoles are covered, particularly those with pharmaceutical applications such as sunitinib (SU11248), the orally active receptor tyrosine kinase inhibitor marketed by Pfizer as Sutent®. Traditional synthetic approaches to 3‐alkenyl‐oxindoles are summarised and then recently developed tandem/telescoped synthetic routes are described.

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“…(The estimates of DEMoss and EVANs (1959) employed a molecular weight of 357, which was in error. The molecular extinction coefficients calculated by the latter authors from weight determinations should be increased by a factor of about 1.04).Structural studies were largely unsuccessful until a remarkable series of experiments reported from the University of Liverpool (BALLANTINE et al, 1958). The structure of violacein ( Fig.…”

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confidence: 97%

“…Although it may be argued that the minor component, the indolyl-derivative, is an artifact of isolation, the possibility seems unlikely because the two components are not interconvertible after separation, even when subjected to the same purification treatment. The blue and purple components referred to by DEMoss and EVANS (1959) undoubtedly correspond to violacein (the 5-hydroxyindolyl derivative) and deoxyviolacein (5 -(3 -indolyl) -3 -(3 -oxindol ylidene) -2-oxopyrroline) (BALLANTINE et al, 1958), respectively.The biosynthetic pathway of pigment synthesis is unknown, although all of the carbon and nitrogen atoms of violacein are probably derived exclusively from L-tryptophan. Studies of the nutritional and physiological requirements for growth and pigment synthesis have been reported (DEMoss and HAPPEL, 1959; EVANS, 1959, 1960).…”

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Biosynthesis

1967

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All rights, especially that of translation into f oreign 1anguages, reserved. It is also forbidden to reproduce this book, either who1e or in part, by photomechanical means (photostat, microfilm and/or microcard) or by other procedure without written pennission from Springcr-Vcrlag Berlin Heide1bCig GmbH. DedicationFor most areas of scientific pursuit, there is usually that rare investigator who has the imagination to conceive ideas, who has faith in his visions, and who has the ability to critically test his concepts in the laboratory. Almost invariably, this scientist also inspires younger men to enthusiastically enter into his research program. To him should go the accolades and the recognitions of the esteem in which he is held. As only a small part of this esteem, we wish to dedicate these books to Professor SELMAN A. W AKSMAN in appreciation of his leadership and contributions in all facets of antibiotic research. PrefaceThe idea for publishing these books on the mechanism of action and on the biosynthesis of antibiotics was born of frustration in our attempts to keep abreast of the literature. Gone were the years when we were able to keep a bibliography on antibiotics and feel confident that we could find everything that was being published on this sUbject. These fields of investigation were moving forward so rapidly and were encompassing so wide a range of specialized areas in microbiology and chemistry that it was almost impossible to keep abreast of developments. In our naivete and enthusiasm, however, we were unaware that we were toying with an idea that might enmesh us, that we were creating an entity with a life of its own, that we were letting loose a Golom who instead of being our servant would be our master.That we set up ideals for these books is obvious; they would be current guides to developments and information in the areas of mechanism of action and biosynthesis of antibiotics. For almost every subject, we wished to enlist the aid of an investigator who himself had played a part in determining the nature of the phenomena that were being discussed. One concept for the books was that they include only antibiotics for which a definitive, well-documented mechanism of action or biosynthetic pathway was known. Yet, such an approach would not entirely serve the purpose we projected, for it would not encompass all of the information available in these fields of antibiotic investigations and blind searches for the original literature would still have to be made. We therefore chose to include any and all antibiotics about which some pertinent information had been published. It was obvious even at the start that such a compilation, integration, and analysis of information could never be complete unless scientific investigations ceased at the moment the last manuscript was submitted-an end that was neither desirable nor possible. An addendum was therefore included at the end of the volume and left open for the addition of new information until the last pages of the regular articles had been printed.The...

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459. The chemistry of bacteria. Part VIII. The synthesis of violacein and related compounds

Cited by 27 publications

References 0 publications

The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins

The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins

3‐Alkenyl‐oxindoles: Natural Products, Pharmaceuticals, and Recent Synthetic Advances in Tandem/Telescoped Approaches

Biosynthesis

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