DOCSLIB.ORG

Biotechnological Activities and Applications of Bacterial Pigments Violacein and Prodigiosin Seong Yeol Choi1†, Sungbin Lim1†, Kyoung-Hye Yoon2*, Jin I

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Biotechnological Activities and Applications of Bacterial Pigments Violacein and Prodigiosin Seong Yeol Choi1†, Sungbin Lim1†, Kyoung-Hye Yoon2*, Jin I Choi et al. Journal of Biological Engineering (2021) 15:10 https://doi.org/10.1186/s13036-021-00262-9 REVIEW Open Access Biotechnological Activities and Applications of Bacterial Pigments Violacein and Prodigiosin Seong Yeol Choi1†, Sungbin Lim1†, Kyoung-hye Yoon2*, Jin I. Lee3* and Robert J. Mitchell1* Abstract In this review, we discuss violacein and prodigiosin, two chromogenic bacterial secondary metabolites that have diverse biological activities. Although both compounds were “discovered” more than seven decades ago, interest into their biological applications has grown in the last two decades, particularly driven by their antimicrobial and anticancer properties. These topics will be discussed in the first half of this review. The latter half delves into the current efforts of groups to produce these two compounds. This includes in both their native bacterial hosts and heterogeneously in other bacterial hosts, including discussing some of the caveats related to the yields reported in the literature, and some of the synthetic biology techniques employed in this pursuit. Keywords: Prodigiosin, Violacein, Antibacterial, Anticancer, Secondary Metabolite, Production, Synthetic Biology Introduction compound is their cost, which range from $360 to $760 Bacterial strains are capable of producing many different per milligram [4]. Within this review, therefore, discus- secondary metabolites, including anti-cancer and anti- sion will be given primarily to the biological activities of biotic drugs. Here, we discuss two such compounds that these compounds, focusing on ecological and medical are gaining interest due to their diverse biological activ- considerations of both violacein and prodigiosin, as well ities, namely violacein and prodigiosin. Both of these as current methods to over-produce these remarkable compounds are synthesized by Gram-negative hosts and compounds. have been shown in studies from a wide berth of groups to possess important biological activities, including as Violacein and Prodigiosin – Hydrophobic Bacterial potent antibiotics against multidrug resistant pathogens. Chromogenic Pigments Although both compounds were “discovered” nearly a th Prodigiosin and violacein are both colorful secondary century ago in the mid-20 century [1–3], their bio- metabolites, a trait that makes isolating and identify- logical activities are still being studied to this day. How- ing the bacterial strains that produce these com- ever, one critical factor limiting research with either pounds in sufficient quantities easier. As shown in * Correspondence: [email protected]; [email protected]; Fig. 1, violacein is a purple-hued bacterial pigment. [email protected] The fact that this compound is produced by a range † Seong Yeol Choi and Sungbin Lim contributed equally to this work. of natural bacterial strains [5–8], including Chromo- 2Department of Physiology, Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do, South Korea bacterium [9]andJanthinobacterium [10], and in a 3Division of Biological Science and Technology, College of Science and wide-array of environmental locales, including the Technology, Yonsei University, Mirae Campus, Wonju, Gangwon-do, South deep seas [11], rivers [9, 12], agricultural and forest Korea 1School of Life Sciences, Ulsan National Institute of Science and Technology soils [8, 13, 14], within polar and alpine glacial (UNIST), Ulsan 44919, South Korea regions [7, 15, 16],andevenontheleavesofwhite © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Choi et al. Journal of Biological Engineering (2021) 15:10 Page 2 of 16 Fig. 1 Violacein and prodigiosin, showing the chemical structure and the colored phenotypes of the bacterial strains that produce these compounds clover [17] and the skin of amphibians [18], all sug- aerogenes IAM1183 and Citrobacter freundii ACCC gest the production of violacein should be relatively 05411, with no clear detriment to the growth or viability advantageous for the host. However, the octanol- of these strains [59–62] supports this further. However, water partitioning coefficient (Log POW) for violacein individual studies from some groups recently claim vio- is 3.34 [19, 20], classifying this compound as highly lacein exhibits low MIC or growth inhibitory activities hydrophobic and suggesting it is not readily secreted with Gram-negative strains [63–65]. Given the histor- by the host into the surrounding environment. icity and wide range of reports suggesting otherwise, the Similarly, prodigiosin is vibrant red in color (Fig. 1) veracity of these studies needs to be demonstrated inde- and is produced by a number of different Gram-negative pendently by other research groups. and Gram-positive bacterial strains, including Serratia In contrast, the activity of violacein against many dif- marcescens [21] and Streptomyces. As a compound, pro- ferent Gram-positive bacterial strains (Table 1), includ- digiosin is a member of the prodiginines, a group of che- ing Staphylococcus, Bacillus and Streptococcus [3, 40], is micals with the same parent nucleus but differing side well established. Despite this, its spectrum does not groups. For this review, emphasis will be given primarily extend to all Gram-positive strains. For instance, Entero- to prodigiosin as this is the most extensively studied coccus faecalis ATCC 29212 was not affected by the compound within this group. When compared with addition of violacein [66], while Corynebacterium gluta- violacein, prodigiosin is even more hydrophobic, with a micum ATCC 21850 was genetically engineered to Log POW of 5.16 [22]. produce violacein [67]. It also exhibits antibiotic activ- ities against Mycobacterium tuberculosis and M. smeg- Violacein and Prodigiosin as Antimicrobials matis, which are acid-fast microbes, and the Gram- The antimicrobial activities of these two compounds variable Micrococcus luteus [7, 68]. have been extensively studied (Tables 1 and 2), particu- Stemming from its recognized activities against Gram- larly for violacein. It is historically recognized that very positive strains, many recent studies have evaluated the few Gram-negative bacteria are susceptible to violacein, use of violacein against antibiotic-resistant strains of S. data that is supported by independent groups in many aureus [8, 41, 58, 66]. For instance, the minimal inhibi- recent studies [3, 39–41, 58]. The fact that violacein has tory concentrations (MICs) for several S. aureus associ- been produced in recombinant strains of E. coli, as well ated with Bovine Mastitis were between 6.25 and 25.00 as in Salmonella typhimurium VNP20009, Enterobacter μM violacein, even though these strains displayed Choi et al. Journal of Biological Engineering (2021) 15:10 Page 3 of 16 Table 1 Prodigiosin’s antibiotic activity against microorganisms Microbe Description Reference Bacteria Bacillus cereus [23] Bacillus subtilis [24] Enterobacter cloacae [25] Escherichia coli [23, 25][26] Klebsiella aerogenes Human pathogen [25] Pseudomonas aeruginosa Human pathogen [25] Staphylococcus aureus Human pathogen [23, 25–27] Streptococcus pyogenes Human pathogen [27] Fungi Batrachochytrium dendrobatidis Amphibian pathogen [28] Batrachochytrium salamandrivorans Amphibian pathogen [28] Botrytis cinerea Plant pathogen [29] Fusarium oxysporum Plant pathogen [30] Mucor irregularis Human pathogen [31] Mycosphaerella fijiensis Plant pathogen [32] Phytophthora infestans Plant pathogen [30] Pythium myriotylum Plant pathogen [30] Rhizoctonia solani Plant pathogen [30, 33] Sclerotium rolfsii Plant pathogen [30] Virus HSV-1 Herpes [34] Protozoa Plasmodium falciparum Malaria [35, 36] Trypanosoma cruzi Parasitic euglenoids [37] Insect Aedes aegypti Yellow fever mosquito [38] Anopheles stephensi Malaria vector [38] penicillin, ampicillin and/or intermediary erythromycin into a bacterial culture, prodigiosin and violacein rapidly resistance [58]. Moreover, violacein acted synergistically insert into the membranes of the microbe and disrupt with penicillin [58], an idea that was expanded on in an- their integrity, leading to ATP and protein leakage [22, 69, other study [64]. A separate study using methicillin- 70]. Interactions between violacein and bacterial mem- resistant S. aureus (MRSA) reported MICs in basically branes were recently modeled [70], and suggested that this the same range, i.e., 7.5 to 30 μM[66], while research compound does not embed very deeply within the lipid bi- from our group found a multidrug-resistant
Load more

Recommended publications
  • How I Treat Myelofibrosis
    From www.bloodjournal.org by guest on October 7, 2014. For personal use only. Prepublished online September 16, 2014; doi:10.1182/blood-2014-07-575373 How I treat myelofibrosis Francisco Cervantes Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml Advance online articles have been peer reviewed and accepted for publication but have not yet appeared in the paper journal (edited, typeset versions may be posted when available prior to final publication). Advance online articles are citable and establish publication priority; they are indexed by PubMed from initial publication. Citations to Advance online articles must include digital object identifier (DOIs) and date of initial publication. Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved. From www.bloodjournal.org by guest on October 7, 2014. For personal use only. Blood First Edition Paper, prepublished online September 16, 2014; DOI 10.1182/blood-2014-07-575373 How I treat myelofibrosis By Francisco Cervantes, MD, PhD, Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain Correspondence: Francisco Cervantes, MD, Hematology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. Phone: +34 932275428.
    [Show full text]
  • A Genochemetic Strategy for Derivatization of the Violacein Natural Product Scaffold
    bioRxiv preprint doi: https://doi.org/10.1101/202523; this version posted December 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. A GenoChemetic strategy for derivatization of the violacein natural product scaffold Hung-En Lai1#, Alan M. C. Obled4, Soo Mei Chee1,3, Rhodri M. Morgan2, Rosemary Lynch4, Sunil V. Sharma4, Simon J. Moore1^, Karen M. Polizzi5, Rebecca J. M. Goss*4, 1,3, 6 Paul S. Freemont* 1Section of Structural and Synthetic Biology, Department of Infectious Disease, Imperial College London, London SW7 2AZ, UK. 2Department of Life Sciences, Imperial College London, London SW7 2AZ, UK. 3London Biofoundry, Imperial College Translation & Innovation Hub, London, W12 0BZ, UK 4School of Chemistry and Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK. 5Department of Chemical Engineering, Imperial College London, London SW7 2AZ, UK. 6UK DRI Care Research and Technology Centre, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK. *Correspondence: [email protected]; [email protected] ^current address School of Biosciences, University of Kent, Canterbury, CT7 2NJ #current address School of Biological Sciences, Victoria University of Wellington, Wellington 6011, New Zealand. Lead Contact: [email protected] Keywords Violacein, antibiotics biosynthesis, natural product analogue, rebeccamycin, bisindole, halogenase, cross-coupling, GenoChemetics Abstract Natural products and their analogues are often challenging to synthesise due to their complex scaffolds and embedded functional groups.
    [Show full text]
  • Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives
    cancers Review Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives Shirin Hafezi 1 and Mohamed Rahmani 1,2,* 1 Research Institute of Medical & Health Sciences, University of Sharjah, P.O. Box 27272 Sharjah, United Arab Emirates; [email protected] 2 Department of Basic Medical Sciences, College of Medicine, University of Sharjah, P.O. Box 27272 Sharjah, United Arab Emirates * Correspondence: [email protected]; Tel.: +971-6505-7759 Simple Summary: Apoptosis, a programmed form of cell death, represents the main mechanism by which cells die. Such phenomenon is highly regulated by the BCL-2 family of proteins, which includes both pro-apoptotic and pro-survival proteins. The decision whether cells live or die is tightly controlled by a balance between these two classes of proteins. Notably, the pro-survival Bcl-2 proteins are frequently overexpressed in cancer cells dysregulating this balance in favor of survival and also rendering cells more resistant to therapeutic interventions. In this review, we outlined the most important steps in the development of targeting the BCL-2 survival proteins, which laid the ground for the discovery and the development of the selective BCL-2 inhibitor venetoclax as a therapeutic drug in hematological malignancies. The limitations and future directions are also discussed. Abstract: The major form of cell death in normal as well as malignant cells is apoptosis, which is a programmed process highly regulated by the BCL-2 family of proteins. This includes the antiapoptotic proteins (BCL-2, BCL-XL, MCL-1, BCLW, and BFL-1) and the proapoptotic proteins, which can be divided into two groups: the effectors (BAX, BAK, and BOK) and the BH3-only proteins Citation: Hafezi, S.; Rahmani, M.
    [Show full text]
  • Discovery of Mcl-1 Inhibitors from Integrated High Throughput and Virtual Screening Received: 9 March 2018 Ahmed S
    www.nature.com/scientificreports OPEN Discovery of Mcl-1 inhibitors from integrated high throughput and virtual screening Received: 9 March 2018 Ahmed S. A. Mady1,3, Chenzhong Liao1,8, Naval Bajwa1,9, Karson J. Kump1,4, Accepted: 5 June 2018 Fardokht A. Abulwerdi 1,3,10, Katherine L. Lev1, Lei Miao 1, Sierrah M. Grigsby1,2, Published: xx xx xxxx Andrej Perdih5, Jeanne A. Stuckey6, Yuhong Du7, Haian Fu 7 & Zaneta Nikolovska-Coleska1,2,3,4 Protein-protein interactions (PPIs) represent important and promising therapeutic targets that are associated with the regulation of various molecular pathways, particularly in cancer. Although they were once considered “undruggable,” the recent advances in screening strategies, structure-based design, and elucidating the nature of hot spots on PPI interfaces, have led to the discovery and development of successful small-molecule inhibitors. In this report, we are describing an integrated high-throughput and computational screening approach to enable the discovery of small-molecule PPI inhibitors of the anti- apoptotic protein, Mcl-1. Applying this strategy, followed by biochemical, biophysical, and biological characterization, nineteen new chemical scafolds were discovered and validated as Mcl-1 inhibitors. A novel series of Mcl-1 inhibitors was designed and synthesized based on the identifed difuryl-triazine core scafold and structure-activity studies were undertaken to improve the binding afnity to Mcl- 1. Compounds with improved in vitro binding potency demonstrated on-target activity in cell-based studies. The obtained results demonstrate that structure-based analysis complements the experimental high-throughput screening in identifying novel PPI inhibitor scafolds and guides follow-up medicinal chemistry eforts.
    [Show full text]
  • BCL-2 Inhibitors for Chronic Lymphocytic Leukemia
    L al of euk rn em u i o a J Robak, J Leuk 2015, 3:3 Journal of Leukemia DOI: 10.4172/2329-6917.1000e114 ISSN: 2329-6917 Editorial Open access BCL-2 inhibitors for Chronic Lymphocytic Leukemia Tadeusz Robak* Department of Hematology, Medical University of Lodz, 93-510 Lodz, ul, Ciolkowskiego 2, Poland *Corresponding author: Tadeusz Robak, Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, 93-510 Lodz, Ul. Ciolkowskiego 2, Poland, Tel: +48 42 6895191; E-mail: [email protected] Rec date: August 10, 2015; Acc date: August 12, 2015; Pub date: August 24, 2015 Copyright: © 2015 Robak T. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Editorial cyclophosphamide and rituximab (FCR) or bendamustin-rituximab (BR) regimens in refractory CLL are ongoing (NCT00868413). B-cell chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Europe and North America, with an annual Venetoclax ( GDC-0199, ABT-199, RG7601; Genentech, South San incidence of three to five cases per 100,000 [1]. The approval of Francisco, CA), is a first-in-class, orally bioavailable BCL-2 family rituximab-based immunochemotherapy represented a substantial protein inhibitor that binds with high affinity to BCL-2 and with lower therapeutic advance in CLL [2]. However, currently available therapies affinity to the other BCL-2 family proteins Bcl-xL, Bcl-w and Mcl-1 are only partially efficient, and there is an obvious need to develop [14].
    [Show full text]
  • High Crude Violacein Production from Glucose by Escherichia Coli
    Fang et al. Microbial Cell Factories (2015) 14:8 DOI 10.1186/s12934-015-0192-x RESEARCH Open Access High crude violacein production from glucose by Escherichia coli engineered with interactive control of tryptophan pathway and violacein biosynthetic pathway Ming-Yue Fang1, Chong Zhang1*,SongYang2, Jin-Yu Cui2, Pei-Xia Jiang3, Kai Lou4, Masaaki Wachi5 and Xin-Hui Xing1* Abstract Background: As bacteria-originated crude violacein, a natural indolocarbazole product, consists of violacein and deoxyviolacein, and can potentially be a new type of natural antibiotics, the reconstruction of an effective metabolic pathway for crude violacein (violacein and deoxyviolacein mixture) synthesis directly from glucose in Escherichia coli was of importance for developing industrial production process. Results: Strains with a multivariate module for varied tryptophan productivities were firstly generated by combinatorial knockout of trpR/tnaA/pheA genes and overexpression of two key genes trpEfbr/trpD from the upstream tryptophan metabolic pathway. Then, the gene cluster of violacein biosynthetic pathway was introduced downstream of the generated tryptophan pathway. After combination of these two pathways, maximum crude violacein production directly from glucose by E. coli B2/pED + pVio was realized with a titer of 0.6 ± 0.01 g L−1 in flask culture, which was four fold higher than that of the control without the tryptophan pathway up-regulation. In a 5-L bioreactor batch fermentation with glucose as the carbon source, the recombinant E. coli B2/pED + pVio exhibited a crude violacein titer of 1.75 g L−1 and a productivity of 36 mg L−1 h−1, which was the highest titer and productivity reported so far under the similar culture conditions without tryptophan addition.
    [Show full text]
  • Phenotype-Based Drug Screening Reveals Association Between Venetoclax Response and Differentiation Stage in Acute Myeloid Leukemia
    Acute Myeloid Leukemia SUPPLEMENTARY APPENDIX Phenotype-based drug screening reveals association between venetoclax response and differentiation stage in acute myeloid leukemia Heikki Kuusanmäki, 1,2 Aino-Maija Leppä, 1 Petri Pölönen, 3 Mika Kontro, 2 Olli Dufva, 2 Debashish Deb, 1 Bhagwan Yadav, 2 Oscar Brück, 2 Ashwini Kumar, 1 Hele Everaus, 4 Bjørn T. Gjertsen, 5 Merja Heinäniemi, 3 Kimmo Porkka, 2 Satu Mustjoki 2,6 and Caroline A. Heckman 1 1Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki; 2Hematology Research Unit, Helsinki University Hospital Comprehensive Cancer Center, Helsinki; 3Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; 4Department of Hematology and Oncology, University of Tartu, Tartu, Estonia; 5Centre for Cancer Biomarkers, De - partment of Clinical Science, University of Bergen, Bergen, Norway and 6Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland ©2020 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2018.214882 Received: December 17, 2018. Accepted: July 8, 2019. Pre-published: July 11, 2019. Correspondence: CAROLINE A. HECKMAN - [email protected] HEIKKI KUUSANMÄKI - [email protected] Supplemental Material Phenotype-based drug screening reveals an association between venetoclax response and differentiation stage in acute myeloid leukemia Authors: Heikki Kuusanmäki1, 2, Aino-Maija
    [Show full text]
  • Identifying the Druggable Interactome of EWS-FLI1 Reveals MCL-1 Dependent Differential Sensitivities of Ewing Sarcoma Cells to Apoptosis Inducers
    www.oncotarget.com Oncotarget, 2018, Vol. 9, (No. 57), pp: 31018-31031 Research Paper Identifying the druggable interactome of EWS-FLI1 reveals MCL-1 dependent differential sensitivities of Ewing sarcoma cells to apoptosis inducers Kalliopi Tsafou1,7,*, Anna Maria Katschnig3,*, Branka Radic-Sarikas2,3,*, Cornelia Noëlle Mutz3, Kristiina Iljin5, Raphaela Schwentner3, Maximilian O. Kauer3, Karin Mühlbacher3, Dave N.T. Aryee3,4, David Westergaard1, Saija Haapa-Paananen5, Vidal Fey5, Giulio Superti-Furga2, Jeffrey Toretsky6, Søren Brunak1 and Heinrich Kovar3,4 1Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark 2CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria 3Children’s Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria 4Department of Pediatrics, Medical University of Vienna, Vienna, Austria 5Medical Biotechnology, VTT Technical Research Centre of Finland, Espoo, Finland 6Department of Oncology, Georgetown University, Medical Center, Washington, DC, USA 7Current address: Broad Institute of MIT and Harvard, Cambridge, MA, USA *These authors contributed equally to this work Correspondence to: Heinrich Kovar, email: [email protected] Keywords: high-throughput compound screening; Ewing sarcoma; drug-target network; apoptosis; BCL-2 inhibitors Received: March 07, 2018 Accepted: June 22, 2018 Published: July 24, 2018 Copyright: Tsafou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Ewing sarcoma (EwS) is an aggressive pediatric bone cancer in need of more effective therapies than currently available.
    [Show full text]
  • Antiplasmodial and Trypanocidal Activity of Violacein and Deoxyviolacein Produced from Synthetic Operons Elizabeth Bilsland1,2,3* , Tatyana A
    Bilsland et al. BMC Biotechnology (2018) 18:22 https://doi.org/10.1186/s12896-018-0428-z RESEARCH ARTICLE Open Access Antiplasmodial and trypanocidal activity of violacein and deoxyviolacein produced from synthetic operons Elizabeth Bilsland1,2,3* , Tatyana A. Tavella3, Renata Krogh4, Jamie E. Stokes5, Annabelle Roberts1, James Ajioka6, David R. Spring5, Adriano D. Andricopulo4, Fabio T. M. Costa3 and Stephen G. Oliver1 Abstract Background: Violacein is a deep violet compound that is produced by a number of bacterial species. It is synthesized from tryptophan by a pathway that involves the sequential action of 5 different enzymes (encoded by genes vioAto vioE). Violacein has antibacterial, antiparasitic, and antiviral activities, and also has the potential of inducing apoptosis in certain cancer cells. Results: Here, we describe the construction of a series of plasmids harboring the complete or partial violacein biosynthesis operon and their use to enable production of violacein and deoxyviolacein in E.coli. We performed in vitro assays to determine the biological activity of these compounds against Plasmodium, Trypanosoma, and mammalian cells. We found that, while deoxyviolacein has a lower activity against parasites than violacein, its toxicity to mammalian cells is insignificant compared to that of violacein. Conclusions: We constructed E. coli strains capable of producing biologically active violacein and related compounds, and propose that deoxyviolacein might be a useful starting compound for the development of antiparasite drugs. Keywords: Violacein, Deoxyviolacein, Plasmodium falciparum, Trypanosoma cruzi, Synthetic operon, Antiparasitic, Escherichia coli Background potential and may represent a chemical scaffold for the Violacein is a violet indolocarbazole pigment that is pro- developemt of clinically useful drugs.
    [Show full text]
  • Engineering Oleaginous Yeast Yarrowia Lipolytica for Violacein Production: Extraction, Quantitative Measurement and Culture Optimization
    bioRxiv preprint doi: https://doi.org/10.1101/687012; this version posted July 2, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Engineering oleaginous yeast Yarrowia lipolytica for violacein production: extraction, quantitative measurement and culture optimization Yingjia Tong1, 2, Jingwen Zhou1, Liang Zhang1*, and Peng Xu2,* 1 School of Biotechnology, Jiangnan University, Wuxi, China 2 Chemical, Biochemical and Environmental Engineering, University of Maryland Baltimore County, Baltimore, MD, USA * Corresponding author Tel: +1(410)-455-2474; fax: +1(410)-455-1049. E-mail address: [email protected] (PX) and [email protected] (LZ) 1 bioRxiv preprint doi: https://doi.org/10.1101/687012; this version posted July 2, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Violacein is a naturally occurring anticancer therapeutic with deep purple color. Yeast fermentation represents an alternative approach to efficiently manufacturing violacein from inexpensive feedstocks. In this work, we optimized the extraction protocol to improve violacein recovery ratio and purity from yeast culture, including the variations of organic solvents, the choice of mechanical shear stress, incubation time and the use of cell wall-degrading enzymes. We also established the quantitative correlation between HPLC and microplate reader method. We demonstrated that both HPLC and microplate reader are technically equivalent to measure violacein from yeast culture. Furthermore, we optimized the yeast cultivation conditions, including carbon/nitrogen ratio and pH conditions.
    [Show full text]
  • Chromobacterium Violaceum ATCC31532 Produces
    bioRxiv preprint doi: https://doi.org/10.1101/589192; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 A chemical counterpunch: Chromobacterium violaceum ATCC31532 produces 2 violacein in response to translation-inhibiting antibiotics 3 4 Gabriel L. Lozano1,2, Changhui Guan2, Yanzhuan Cao2, Bradley R. Borlee3, Nichole A. 5 Broderick4, Eric V. Stabb5, Jo Handelsman1,2 6 7 1 Wisconsin Institute for Discovery and Department of Plant Pathology, University of 8 Wisconsin-Madison 9 2 Department of Molecular, Cellular and Developmental Biology, Yale University 10 3 Department of Microbiology, Immunology and Pathology, Colorado State University 11 4 Department of Molecular and Cell Biology, University of Connecticut 12 5 Department of Microbiology, University of Georgia 13 14 *To whom correspondence should be addressed [email protected] 15 16 1 bioRxiv preprint doi: https://doi.org/10.1101/589192; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 17 ABSTRACT 18 Bacterially produced antibiotics play important roles in microbial interactions and 19 competition. Antibiosis can induce resistance mechanisms in target organisms and may 20 induce other countermeasures as well. Here, we show that hygromycin A from 21 Streptomyces sp.
    [Show full text]
  • Marine Natural Products from Tunicates and Their Associated Microbes
    marine drugs Review Marine Natural Products from Tunicates and Their Associated Microbes Chatragadda Ramesh 1,2,*, Bhushan Rao Tulasi 3, Mohanraju Raju 2, Narsinh Thakur 4 and Laurent Dufossé 5,* 1 Biological Oceanography Division (BOD), CSIR-National Institute of Oceanography (CSIR-NIO), Dona Paula 403004, India 2 Department of Ocean Studies and Marine Biology, Pondicherry Central University, Brookshabad Campus, Port Blair 744102, India; [email protected] 3 Zoology Division, Sri Gurajada Appa Rao Government Degree College, Yellamanchili 531055, India; [email protected] 4 Chemical Oceanography Division (COD), CSIR-National Institute of Oceanography (CSIR-NIO), Dona Paula 403004, India; [email protected] 5 Laboratoire de Chimie et Biotechnologie des Produits Naturels (CHEMBIOPRO), Université de La Réunion, ESIROI Agroalimentaire, 15 Avenue René Cassin, CS 92003, CEDEX 9, F-97744 Saint-Denis, Ile de La Réunion, France * Correspondence: [email protected] (C.R.); [email protected] (L.D.); Tel.: +91-(0)-832-2450636 (C.R.); +33-668-731-906 (L.D.) Abstract: Marine tunicates are identified as a potential source of marine natural products (MNPs), demonstrating a wide range of biological properties, like antimicrobial and anticancer activities. The symbiotic relationship between tunicates and specific microbial groups has revealed the acquisi- tion of microbial compounds by tunicates for defensive purpose. For instance, yellow pigmented compounds, “tambjamines”, produced by the tunicate, Sigillina signifera (Sluiter, 1909), primarily Citation: Ramesh, C.; Tulasi, B.R.; originated from their bacterial symbionts, which are involved in their chemical defense function, indi- Raju, M.; Thakur, N.; Dufossé, L. cating the ecological role of symbiotic microbial association with tunicates. This review has garnered Marine Natural Products from comprehensive literature on MNPs produced by tunicates and their symbiotic microbionts.
    [Show full text]