| Reference | [1]. Appl Microbiol Biotechnol. 2014 May;98(9):3841-58. doi:
10.1007/s00253-014-5590-1. Epub 2014 Feb 23.
<br>
Properties and applications of undecylprodigiosin and other bacterial
prodigiosins.
<br>
Stankovic N(1), Senerovic L, Ilic-Tomic T, Vasiljevic B, Nikodinovic-Runic J.
<br>
Author information:
(1)Institute of Molecular Genetics and Genetic Engineering, University of
Belgrade, Vojvode Stepe 444a, P.O. Box 23, 11000, Belgrade, Serbia.
<br>
The growing demand to fulfill the needs of present-day medicine in terms of
novel effective molecules has lead to reexamining some of the old and known
bacterial secondary metabolites. Bacterial prodigiosins (prodiginines) have a
long history of being re markable multipurpose compounds, best examined for
their anticancer and antimalarial activities. Production of prodigiosin in the
most common producer strain Serratia marcescens has been described in great
detail. However, few reports have discussed the ecophysiological roles of these
molecules in the producing strains, as well as their antibiotic and
UV-protective properties. This review describes recent advances in the
production process, biosynthesis, properties, and applications of bacterial
prodigiosins. Special emphasis is put on undecylprodigiosin which has generally
been a less studied member of the prodigiosin family. In addition, it has been
suggested that proteins involved in undecylprodigiosin synthesis, RedG and RedH,
could be a useful addition to the biocatalytic toolbox being able to mediate
regio- and stereoselective oxidative cyclization. Judging by the number of
recent references (216 for the 2007-2013 period), it has become clear that
undecylprodigiosin and other bacterial prodigiosins still hold surprises in
terms of valuable properties and applicative potential to medical and other
industrial fields and that they still deserve continuing research curiosity.
<br>
DOI: 10.1007/s00253-014-5590-1
PMID: 24562326
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<br>
[2]. PLoS One. 2020 Jul 14;15(7):e0236282. doi: 10.1371/journal.pone.0236282.
eCollection 2020.
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Correction: Undecylprodigiosin Induced Apoptosis in P388 Cancer Cells Is
Associated with Its Binding to Ribosome.
<br>
Liu P, Wang YY, Qi X, Gu Q, Geng M, Li J.
<br>
Erratum for
PLoS One. 2013 Jun 14;8(6):e65381.
<br>
[This corrects the article DOI: 10.1371/journal.pone.0065381.].
<br>
DOI: 10.1371/journal.pone.0236282
PMCID: PMC7360054
PMID: 32663232
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<br>
[3]. DNA Cell Biol. 2018 Jun;37(6):535-542. doi: 10.1089/dna.2018.4161. Epub 2018 Apr
19.
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Unlike Butylcycloheptylprodigiosin, Isolated Undecylprodigiosin from
Streptomyces parvulus Is Not a MDR1 and BCRP Substrate in Multidrug-Resistant
Cancers.
<br>
Mirzaei SA(1)(2), Safari Kavishahi M(1), Keshavarz Z(1), Elahian F(1)(2).
<br>
Author information:
(1)1 Department of Medical Biotechnology, School of Advanced Technologies,
Shahrekord University of Medical Sciences , Shahrekord, Iran .
(2)2 Cellular and Molecular Research Center, Basic Health Sciences Institute,
Shahrekord University of Medical Sciences , Shahrekord, Iran .
<br>
The search for new chemotherapeutics unaffected by efflux pumps would
significantly increase life expectancy in patients with malignant cancers. In
this study, butylcycloheptylprodigiosin and undecylprodigiosin were
HPLC-purified and verified, using nuclear magnetic resonance spectroscopy. Cell
cytotoxicity and transportation kinetics on multiple-drug resistance (MDR) cells
were evaluated. Daunorubicin and butylcycloheptylprodigiosin were less toxic in
the MDR1 overexpressing line, but undecylprodigiosin revealed potent toxicity
toward MDR1 and BCRP expressing malignant cells. There was no noticeable change
in MDR1 and BCRP transcripts during 3 days of treatment with prodiginines. While
daunorubicin and mitoxantrone uptake from the cell environment significantly
decreased with increasing multidrug resistance up to 46% and 62%, respectively,
the accumulation of undecylprodigiosin and to a lesser extent
butylcycloheptylprodigiosin in the resistance cells occurred cell- and
dose-dependently via a passive diffusion process and were almost equally
sensitive to the parent lines. The efflux of xenobiotics commenced immediately
with different kinetics in various cells. A greater amount of daunorubicin and
mitoxantrone were rapidly thrown out of their corresponding MDR cells in the
absence of the specific inhibitor (3.01 and 1.81 dF/min, respectively) and
represented functional efflux pumps. MDR pumps did not apparently influence
undecylprodigiosin efflux patterns; but butylcycloheptylprodigiosin was
partially removed from EPG85.257RDB cells at the rate of 2.66 and 1.41 dF/min in
the absence and presence of verapamil, respectively.
<br>
DOI: 10.1089/dna.2018.4161
PMID: 29672160
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[4]. J Am Chem Soc. 2015 Jun 24;137(24):7889-97. doi: 10.1021/jacs.5b03994. Epub 2015
Jun 12.
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Stereochemistry and Mechanism of Undecylprodigiosin Oxidative Carbocyclization
to Streptorubin B by the Rieske Oxygenase RedG.
<br>
Withall DM(1), Haynes SW(1), Challis GL(1).
<br>
Author information:
(1)Department of Chemistry, University of Warwick, Coventry CV4 7AL, United
Kingdom.
<br>
The prodiginines are a group of specialized metabolites that share a
4-methoxypyrrolyldipyrromethene core structure. Streptorubin B is a structurally
remarkable member of the prodiginine group produced by Streptomyces coelicolor
A3(2) and other actinobacteria. It is biosynthesized from undecylprodigiosin by
an oxidative carbocyclization catalyzed by the Rieske oxygenase-like enzyme
RedG. Undecylprodigiosin derives from the RedH-catalyzed condensation of
2-undecylpyrrole and 4-methoxy-2, 2′-bipyrrole-5-carboxaldehyde (MBC). To probe
the mechanism of the RedG-catalyzed reaction, we synthesized
2-(5-pentoxypentyl)-pyrrole, an analogue of 2-undecylpyrrole with an oxygen atom
next to the site of C-C bond formation, and fed it, along with synthetic MBC, to
Streptomyces albus expressing redH and redG. This resulted in the production of
the 6′-oxa analogue of undecylprodigiosin. In addition, a small amount of a
derivative of this analogue lacking the n-pentyl group was produced, consistent
with a RedG catalytic mechanism involving hydrogen abstraction from the alkyl
chain of undecylprodigiosin prior to pyrrole functionalization. To investigate
the stereochemistry of the RedG-catalyzed oxidative carbocyclization,
[7′-(2)H](7’R)-2-undecylpyrrole and [7′-(2)H](7’S)-2-undecylpyrrole were
synthesized and fed separately, along with MBC, to S. albus expressing redH and
redG. Analysis of the extent of deuterium incorporation into the streptorubin B
produced in these experiments showed that the pro-R hydrogen atom is abstracted
from C-7′ of undecylprodigiosin and that the reaction proceeds with inversion of
configuration at C-7′. This contrasts sharply with oxidative heterocyclization
reactions catalyzed by other nonheme iron-dependent oxygenase-like enzymes, such
as isopenicillin N synthase and clavaminate synthase, which proceed with
retention of configuration at the carbon center undergoing functionalization.
<br>
DOI: 10.1021/jacs.5b03994
PMID: 26023709
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<br>
[5]. J Appl Genet. 2021 Feb;62(1):165-182. doi: 10.1007/s13353-020-00597-x. Epub 2021
Jan 7.
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Enhancement of undecylprodigiosin production from marine endophytic recombinant
strain Streptomyces sp. ALAA-R20 through low-cost induction strategy.
<br>
Alzahrani NH(1), El-Bondkly AAM(2), El-Gendy MMAA(3), El-Bondkly AM(4).
<br>
Author information:
(1)Department of Biology, College of Science, University of Jeddah, Jeddah,
Saudi Arabia.
(2)Faculty of Pharmacy, Cairo University, kasr El-Aini, Cairo, 11562, Egypt.
(3)Chemistry of Natural and Microbial Products Department, National Research
Centre, Dokki, Giza, 12622, Egypt.
(4)Genetics and Cytology Department, National Research Centre, Dokki, Giza,
12622, Egypt. [email protected].
<br>
Genetic manipulation of the undecylprodigiosin-producing strains and engineered
culture medium approaches were applied as the most economical induction strategy
for improving production. The hyper-producing recombinant strain ALAA-R20 was
obtained after applying protoplast fusion strategy between the potent producer
marine endophytic strains Streptomyces sp. ESRAA-10 (P1) and Streptomyces sp.
ESRAA-31 (P2) of Dendronephthya hemprichi. Recombinant strain ALAA-R20 produced
undecylprodigiosin yield higher than its parental strains ESRAA-10 and ESRAA-31
by 82.45% and 105.52% under submerged fermentation using modified R2YE medium.
In order to reduce the costs of producing undecylprodigiosin, a solid-state
fermentation (SSF) was applied. Scaled-up of optimized SSF parameters consisting
of groundnut oil cake (GOC) sized to 3 mm, initial moisture content 80% with a
mixture of dairy mill and fruit processing wastewaters (1:1), pH 7.0, inoculum
size equal to 3 × 105 spores/g dry substrate (gds), incubation temperature
30 °C, and 7-day incubation period yielded the highest yield of 181.78 mg/gds of
undecylprodigiosin by the recombinant strain Streptomyces sp. ALAA-R20.
Extraction and purification of the pigment using the chromatographic techniques
as well as mass spectral analysis exhibited maximum absorbance at 539 nm which
is physiological property of the undecylprodigiosin. Undecylprodigiosin was
stable over a wide temperature ranged from - 20 to 35 °C even after storage for
6 months. The maximum yield and stability of pigment was obtained at the acidic
pH (acidified methanol, pH 4.0). Undecylprodigiosin obtained from the
recombinant strain Streptomyces sp. ALAA-R20 demonstrated strong antimicrobial
activity against all multidrug-resistant bacterial and fungal strains tested
with minimum inhibitory, minimum bactericidal, and minimum fungicidal
concentrations ranged between 0.5 and 4.0, 0.5 to 4.0, and 1.0 to 8.0 μg/mL,
respectively. It also showed complete inhibition of cancer cells; HCT-116,
HepG-2, MCF-7 and A-549 at 5, 8, 4, and 7 μM with IC50 equal to 2.0, 4.7, 1.2,
and 2.8 μM, respectively.
<br>
DOI: 10.1007/s13353-020-00597-x
PMID: 33415709
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