Kegg Pathway: Carbazole degradation

Bioresour Technol. 2010 Jan; 101(1): 174-80
Tan Y, Ji G

Status of, and changes in, the bacterial communities at two acclimation stages (with- and without-ultrasound) in a small 70 degrees C ultrasound-enhanced anaerobic reactor for treating Carbazole-containing wastewater reactor were analyzed by PCR-DGGE and real-time PCR techniques. PCR-DGGE results indicated that a large number of bands occurred in the whole sludge samples. Pseudomonas sp., Comamonas sp., and Diaphorobacter sp. were identified as being able to utilize Carbazole as a carbon source, survive in an anaerobic and ultra-high-temperature environment and become dominant bacterial taxa during the with-ultrasound stage in the reactor. Total bacterial density in the with-ultrasonic stages was 10 x higher than in the without-ultrasonic treatment. The proportion of Pseudomonas was relatively stable at 0.13%-0.15% in both acclimation stages, which indicates that Pseudomonas can flourish and promote Carbazole degradation either with or without-ultrasound. These studies provide information on Carbazole degradation under ultra-high-temperature conditions in an anaerobic environment.

Clin Oral Implants Res. 2009 Oct; 20(10): 1116-23
Kozlovsky A, Aboodi G, Moses O, Tal H, Artzi Z, Weinreb M, Nemcovsky CE

OBJECTIVE: The aim of this study was to evaluate histologically the bio-degradation of two layers of Bio-Gide((R)) (BG) membrane, as compared with that of a single layer. MATERIAL AND METHODS: Two circular calvarial bony defects, 5 mm in diameter, were made in 24 Wistar rats. BG membrane, labeled with biotin, was cut into 5-mm-diameter disks, and placed in defects either as a mono-layer membrane (MLM) or as a double-layer membrane (DLM). Rats were sacrificed after 4 or 9 weeks and histology was performed. Membranes were stained with horseradish peroxidase-conjugated streptavidin and aminoethyl Carbazole as a substrate for detection of biotinylated collagen. The area of collagen and thickness of the residual membranes were measured by image analysis software. Statistical analysis was performed using the non-parametric Wilcoxon's signed-ranks test. RESULTS: At 4-week collagen area per measurement window within the DLM sites (0.09+/-0.05 mm(2)) was significantly greater (P<0.01) than that in the MLM sites (0.047+/-0.034 mm(2)). At 9 weeks, the collagen area was also greater in the DLM sites (0.037+/-0.026 mm(2)) compared with that of the MLM sites (0.025+/-0.016 mm(2)); however, this difference did not reach statistical significance. The rate of membrane degradation, calculated as percent membrane lost compared with baseline, was similar for the DLM and MLM at both time points ( approximately 60% at 4 weeks and approximately 80% at 9 weeks). In addition, the residual DLM thickness at 4 weeks (475.5+/-73.77 mum) was significantly (P<0.01) greater than that of MLM (262.38+/-48.01 mum). At 9 weeks, membrane thickness was also greater in the DLM sites (318.22+/-70.45 mum) compared with that of the MLM sites (183.32+/-26.72 mum); however, this difference did not reach statistical significance. The reduction in thickness between 4 and 9 weeks was 30% for MLM and 33% for DLM. DISCUSSION: The use of a double layer of BG membrane results in a barrier of increased collagen area and thickness, compared with application of a single layer.

J Mol Biol. 2009 Sep 18; 392(2): 436-51
Inoue K, Ashikawa Y, Umeda T, Abo M, Katsuki J, Usami Y, Noguchi H, Fujimoto Z, Terada T, Yamane H, Nojiri H

Carbazole 1,9a-dioxygenase (CARDO) consists of terminal oxygenase (Oxy), ferredoxin (Fd), and ferredoxin reductase (Red) components and is a member of the Rieske nonheme iron oxygenases. Rieske nonheme iron oxygenases are divided into five subclasses (IA, IB, IIA, IIB, and III) based on the number of constituents and the nature of their redox centers. Each component of a class IIB CARDO from Nocardioides aromaticivorans IC177 was purified, and the interchangeability of the electron transfer reactions with each component from the class III CARDOs was investigated. Despite the fact that the Fds of both classes are Rieske-type, strict specificities between the Oxy and Fd components were observed. On the other hand, the Fd and Red components were interchangeable, even though the Red components differ in cofactor composition; the class IIB Red contains flavin-adenine-dinucleotide (FAD)- and NADH-binding domains, whereas the class III Red has a chloroplast-type [2Fe-2S] cluster in addition to the FAD- and NADH-binding domains. The crystal structures of the class IIB Oxy and Fd components were compared to the previously reported Fd:Oxy complex structure of class III CARDO. This comparison suggested residues in common between class IIB and class III CARDOs that are important for interactions between Fd and Oxy. In the class IIB CARDOs, these included His75 and Glu71 in Fd and Lys20 and Glu357 in Oxy for electrostatic interactions, and Phe74 and Pro90 in Fd and Trp21, Leu359, and Val367 in Oxy for hydrophobic interactions. The residues that formed the interacting surface but were not conserved between classes were thought to be necessary to form the appropriate geometry and to determine electron transfer specificity between Fd and Oxy.

Chem Biol Interact. 2009 Oct 30; 181(3): 447-54
Jönsson ME, Franks DG, Woodin BR, Jenny MJ, Garrick RA, Behrendt L, Hahn ME, Stegeman JJ

The tryptophan photooxidation product 6-formylindolo[3,2-b]Carbazole (FICZ) has been proposed as a physiological ligand for the mammalian aryl hydrocarbon receptor (AHR), which it binds with high-affinity, inducing expression of cytochrome P450 1A1 (CYP1A1). We investigated whether the response to FICZ is evolutionarily conserved in vertebrates by measuring FICZ binding to two zebrafish AHRs (AHR1B and AHR2) and its ability to induce zebrafish CYP1 genes (CYP1A, CYP1B1, CYP1C1, CYP1C2, and CYP1D1) in vivo. Exposure of zebrafish embryos (48 h-post-fertilization; hpf) to 10 nM FICZ for 6h caused strong induction of CYP1A mRNA and a statistically significant but modest induction of CYP1B1 and CYP1C1. Neither CYP1C2 nor CYP1D1 expression was induced by FICZ under the conditions of dose, time or developmental stage examined here. CYP1A induction was significantly greater after 6 h than after 12 h of exposure to FICZ, suggesting a rapid degradation of inducer. The 6-h EC(50) values for induction of CYP1A and CYP1B1 by FICZ were 0.6 and 0.5 nM compared to 72-h EC(50) values of 2.3 and 2.7 nM for PCB126, indicating that in zebrafish embryos FICZ is a more potent inducer than PCB126. FICZ at 10 nM was able to completely displace binding of 2,3,7,8-tetrachloro-1,6[3H]-dibenzo-p-dioxin to in vitro-expressed zebrafish AHR2 and AHR1B. Inhibition of AHR2 translation in zebrafish embryos by an AHR2-specific morpholino antisense oligonucleotide decreased the induction of CYP1A and CYP1B1 by FICZ and by PCB126. Together, these results demonstrate that FICZ is a potent AHR agonist in zebrafish, inducing expression of multiple CYP1 genes largely through AHR2. Evolutionary conservation of the response to FICZ is consistent with a possible role as an endogenous signaling molecule acting through the AHR.

Phys Chem Chem Phys. 2009 Jul 7; 11(25): 5124-9
Gao T, Shi LL, Li HB, Zhao SS, Li H, Sun SL, Su ZM, Lu YH

The combination of genetic algorithm and back-propagation neural network correction approaches (GABP) has successfully improved the calculation accuracy of absorption energies. In this paper, the absorption energies of 160 organic molecules are corrected to test this method. Firstly, the GABP1 is introduced to determine the quantitative relationship between the experimental results and calculations obtained by using quantum chemical methods. After GABP1 correction, the root-mean-square (RMS) deviations of the calculated absorption energies reduce from 0.32, 0.95 and 0.46 eV to 0.14, 0.19 and 0.18 eV for B3LYP/6-31G(d), B3LYP/STO-3G and ZINDO methods, respectively. The corrected results of B3LYP/6-31G(d)-GABP1 are in good agreement with experimental results. Then, the GABP2 is introduced to determine the quantitative relationship between the results of B3LYP/6-31G(d)-GABP1 method and calculations of the low accuracy methods (B3LYP/STO-3G and ZINDO). After GABP2 correction, the RMS deviations of the calculated absorption energies reduce to 0.20 and 0.19 eV for B3LYP/STO-3G and ZINDO methods, respectively. The results show that the RMS deviations after GABP1 and GABP2 correction are similar for B3LYP/STO-3G and ZINDO methods. Thus, the B3LYP/6-31G(d)-GABP1 is a better method to predict absorption energies and can be used as the approximation of experimental results where the experimental results are unknown or uncertain by experimental method. This method may be used for predicting absorption energies of larger organic molecules that are unavailable by experimental methods and by high-accuracy theoretical methods with larger basis sets. The performance of this method was demonstrated by application to the absorption energy of the aldehyde Carbazole precursor.

Phys Chem Chem Phys. 2009 Jun 14; 11(22): 4601-10
Musa KA, Eriksson LA

Diclofenac (DF) is a widely used non-steroid anti-inflammatory drug, associated with a range of side effects. The phototoxicity of DF is studied herein employing computational quantum chemistry at the B3LYP/6-31G(d,p) level of theory. The results show that the drug readily absorbs radiation from the UV-region. The deprotonated form spontaneously dechlorinates from its triplet state leading to ring closure and formation of an active photoproduct: chloroCarbazole acetic acid, CCA. The formed CCA is also photodegraded easily from its deprotonated triplet state. Photodegradation routes of deprotonated CCA are decarboxylation (barrier less than 4.5 kcal mol(-1)) and dechlorination (barrier around 6.2 kcal mol(-1)). The energy barrier required for dechlorination to take place from the neutral from is about 20 kcal mol(-1). The differences between the molecular orbitals of the neutral and the deprotonated forms of DF and CCA and spectra obtained using time-dependent density-functional theory (TD-DFT), in addition to the different radical and oxygenated intermediate species formed during the photodegradation mechanism, are discussed in more detail. The theoretical results obtained herein are in line with the experimental results available to date.

Bioorg Med Chem Lett. 2009 Jul 1; 19(13): 3489-92
Gudmundsson KS, Sebahar PR, Richardson LD, Catalano JG, Boggs SD, Spaltenstein A, Sethna PB, Brown KW, Harvey R, Romines KR

The synthesis and SAR of a series of substituted 1-aminotetrahydroCarbazoles with potent activity against human papillomaviruses are described. Synthetic approaches allowing for variation of the substitution pattern of the tetrahydroCarbazole are outlined and resulting changes in antiviral activity are highlighted. Several compounds with in vitro antiviral activity (W12 antiviral assay) in the low nanomolar range were identified and (1R)-6-bromo-N-[(1R)-1-phenylethyl]-2,3,4,9-tetrahydro-1H-Carbazole-1-amine was selected for further evaluation.

Curr Microbiol. 2009 Aug; 59(2): 154-9
Maeda R, Nagashima H, Zulkharnain AB, Iwata K, Omori T

The novel Carbazole (CAR)-degrading bacterium Lysobacter sp. strain OC7 has been isolated from seawater and can also utilize naphthalene and phenanthrene as its sole carbon and energy source. The CAR-degradative gene cluster was isolated and encoded five complete open reading frames (ORFs) and two truncated ORFs. Among them, four ORFs showed 40-50% similarity with previously reported CAR-degradative genes. Ferredoxin (carAc) and ferredoxin reductase (carAd) genes, which are necessary for the CAR 1,9a-dioxygenase system, were not found in this car gene cluster. The car (OC7) gene transcripts were strongly detected when CAR was provided. However, these transcripts were also detected when naphthalene was provided. The resting cell reaction with Escherichia coli revealed that CarAa(OC7) can use CarAc and CarAd of Pseudomonas resinovorans CA10 as ferredoxin and ferredoxin reductase, respectively, and converted CAR to 2'-aminobiphenyl-2,3-diol. In 13 marine CAR-degrading isolates, only Caulobacter sp. strain OC6 hybridized with the car (OC7) gene cluster probe. This is the first report showing CAR-degradative genes from the genus Lysobacter.

Toxicology. 2009 Jun 30; 261(1-2): 9-18
Henseler RA, Romer EJ, Sulentic CE

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a known disruptor of B-cell differentiation and a ligand for the aryl hydrocarbon receptor (AhR), induces binding of the AhR to dioxin responsive elements (DRE) in sensitive genes. The Ig heavy chain (IgH) gene is a sensitive target of TCDD and may be transcriptionally inhibited by TCDD through inhibition of the 3'IgH transcriptional regulatory region (3'IgHRR). While the 3'IgHRR contains binding sites for several transcription factors, two DRE motifs were also identified which may be responsible for TCDD-induced inhibition of 3'IgHRR activation and may implicate the AhR as an important regulator of IgH expression. The objectives of the present study were to determine if 3'IgHRR modulation is limited to TCDD or if structurally diverse chemicals (AhR ligands and non-AhR ligands) from environmental, industrial, dietary or pharmaceutical origin are also capable of modulating the 3'IgHRR and to verify a correlation between effects on a stable 3'IgHRR reporter and the endogenous IgH protein. Utilizing a CH12.LX mouse B-cell line that stably expresses a 3'IgHRR-regulated transgene, we identified an inhibition of both 3'IgHRR activation and IgH protein expression by the non-dioxin AhR activators indolo(3,2-b)Carbazole, primaquine, carbaryl, and omeprazole which followed a rank order potency for AhR activation supporting a role of the AhR in the transcriptional regulation of the 3'IgHRR and IgH expression. However, modulation of the 3'IgHRR and IgH expression was not limited to AhR activators or to suppressive effects. Hydrogen peroxide and terbutaline had an activating effect and benzyl isothiocyanate was inhibitory. These chemicals are not known to influence the AhR signaling pathway but have been previously shown to modulate humoral immunity and/or transcription factors that regulate the 3'IgHRR. Taken together these results implicate the 3'IgHRR as a sensitive immunological target and are the first to identify altered 3'IgHRR activation by a diverse range of chemicals.

Int J Environ Res Public Health. 2009 Jan; 6(1): 278-309
Seo JS, Keum YS, Li QX

Aromatic compounds are among the most prevalent and persistent pollutants in the environment. Petroleum-contaminated soil and sediment commonly contain a mixture of polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatics. Aromatics derived from industrial activities often have functional groups such as alkyls, halogens and nitro groups. Biodegradation is a major mechanism of removal of organic pollutants from a contaminated site. This review focuses on bacterial degradation pathways of selected aromatic compounds. Catabolic pathways of naphthalene, fluorene, phenanthrene, fluoranthene, pyrene, and benzo[a]pyrene are described in detail. Bacterial catabolism of the heterocycles dibenzofuran, Carbazole, dibenzothiophene, and dibenzodioxin is discussed. Bacterial catabolism of alkylated PAHs is summarized, followed by a brief discussion of proteomics and metabolomics as powerful tools for elucidation of biodegradation mechanisms.

Mutat Res. 2009 Jun 1; 665(1-2): 51-60
Valovicová Z, Marvanová S, Mészárosová M, Srancíková A, Trilecová L, Milcová A, Líbalová H, Vondrácek J, Machala M, Topinka J, Gábelová A

Liver progenitor (oval) cells are a potential target cell population for hepatocarcinogens. Our recent study showed that the liver carcinogens 7H-dibenzo[c,g]Carbazole (DBC) and 5,9-dimethyldibenzo[c,g]Carbazole (DiMeDBC), but not the sarcomagen N-methyldibenzo[c,g]Carbazole (N-MeDBC), induced several cellular events associated with tumor promotion in WB-F344 cells, an in vitro model of liver oval cells [J. Vondracek, L. Svihalkova-Sindlerova, K. Pencikova, P. Krcmar, Z. Andrysik, K. Chramostova, S. Marvanova, Z. Valovicova, A. Kozubik, A. Gabelova, M. Machala, 7H-Dibenzo[c,g]Carbazole and 5,9-dimethyldibenzo[c,g]Carbazole exert multiple toxic events contributing to tumor promotion in rat liver epithelial 'stem-like' cells, Mutat. Res. Fundam. Mol. Mech. Mutagen. 596 (2006) 43-56]. In this study, we focused on the genotoxic effects generated by these dibenzoCarbazoles in WB-F344 cells to better understand the cellular and molecular mechanisms involved in hepatocarcinogenesis. Lower IC(50) values determined for DBC and DiMeDBC, as compared with N-MeDBC, indicated a higher sensitivity of WB-F344 cells towards hepatocarcinogens. Accordingly, DBC produced a dose-dependent DNA-adduct formation resulting in substantial inhibition of DNA replication and transcription. In contrast, DNA-adduct number detected in DiMeDBC-exposed cells was almost negligible, whereas N-MeDBC produced a low level of DNA adducts. Although all dibenzoCarbazoles significantly increased the level of strand breaks (p<0.05) and micronuclei (p<0.001) after 2-h treatment, differences in the kinetics of strand break rejoining were found. The strand break level in DiMeDBC- and N-MeDBC-exposed cells returned to near the background level within 24h after treatment, whereas a relatively high DNA damage level was detected in DBC-treated cells up to 48h after exposure. Additional breaks detected after incubation of DiMeDBC-exposed WB-F344 cells with a repair-specific endonuclease, along with a nearly 3-fold higher level of reactive oxygen species found in these cells as compared with control, suggest a possible role of oxidative stress in DiMeDBC genotoxicity. We demonstrated qualitative differences in the DNA damage profiles produced by hepatocarcinogens DBC and DiMeDBC in WB-F344 cells. Different lesions may trigger distinct cellular pathways involved in hepatocarcinogenesis. The low amount of DNA damage, together with an efficient repair, may explain the lack of hepatocarcinogenicity of N-MeDBC.

Bioorg Med Chem Lett. 2009 Jun 1; 19(11): 3078-80
Barta TE, Barabasz AF, Foley BE, Geng L, Hall SE, Hanson GJ, Jenks M, Ma W, Rice JW, Veal J

In the course of our Heat Shock 90 program, certain Carbazole compounds were identified which had an off-target antiproliferative activity. To understand the off-target activity, we studied one analog with strong activity. We discovered that it had an effect on tubulin polymerization kinetics and was competitive with colchicine. Additional analogs were made, and a number of potent compounds were identified.

Bioorg Med Chem Lett. 2009 Jun 1; 19(11): 3088-92
Jin GH, Lee da Y, Cheon YJ, Gim HJ, Kim do H, Kim HD, Ryu JH, Jeon R

A series of phenylisothioureas were synthesized as inhibitors of NO production in lipopolysaccharide-activated macrophages. We investigated the effect of lipophilic moiety and N- or S-substituents of the phenylisothioureas on the activity. Inhibitory activities of Carbazole-linked phenylisothioureas were superior to the corresponding simple phenylisothiourea derivatives. Among these compounds, 12b having N-ethyl and S-isopropyl groups on phenylisothiourea moiety was the most potent in the inhibition of NO production. They inhibited NO production through the suppression of the LPS-induced translocation of p65 subunit of NF-kappaB and the followed suppression of the iNOS protein and mRNA expression.

Eur J Med Chem. 2009 Aug; 44(8): 3235-52
Lemster T, Pindur U, Lenglet G, Depauw S, Dassi C, David-Cordonnier MH

In the context of the design and synthesis of DNA ligands, some new hetarene annelated Carbazoles were synthesized. As lead structure the intercalating tetracyclic systems pyrido[2,3-a]- and pyrido[4,3-a]-Carbazoles and in one case a thieno[2,3-a]-Carbazole were taken into account. A dialkyl amino amidic chain was introduced to the planar chromophoric system with the intent to generate minor groove binding properties. The cytotoxicity of some compounds was examined by the NCI antitumor screening. Furthermore, biophysical as well as biochemical studies were performed in order to get some information about the DNA-binding properties and inhibition of DNA related functional enzymes of this new series of molecules.

Appl Environ Microbiol. 2009 Jun; 75(12): 3920-9
Takahashi Y, Shintani M, Li L, Yamane H, Nojiri H

We determined the effect of the host on the function and structure of the nearly identical IncP-7 Carbazole-degradative plasmids pCAR1.1 and pCAR1.2. We constructed Pseudomonas aeruginosa PAO1(pCAR1.2) and P. fluorescens Pf0-1Km(pCAR1.2) and compared their growth on Carbazole- and succinate-containing media with that of P. putida KT2440(pCAR1.1). We also assessed the stability of the genetic structures of the plasmids in each of the three hosts. Pf0-1Km(pCAR1.2) showed dramatically delayed growth when Carbazole was supplied as the sole carbon source, while the three strains grew at nearly the same rate on succinate. Among the Carbazole-grown Pf0-1Km(pCAR1.2) cells, two types of deficient strains appeared and dominated the population; such dominance was not observed in the other two strains or for succinate-grown Pf0-1Km(pCAR1.2). Genetic analysis showed that the two deficient strains possessed pCAR1.2 derivatives in which the Carbazole-degradative car operon was deleted or its regulatory gene, antR, was deleted by homologous recombination between insertion sequences. From genomic information and quantitative reverse transcription-PCR analyses of the genes involved in Carbazole mineralization by Pf0-1Km(pCAR1.2), we found that the cat genes on the chromosome of Pf0-1Km, which are necessary for the degradation of catechol (a toxic intermediate in the Carbazole catabolic pathway), were not induced in the presence of Carbazole. The resulting accumulation of catechol may have enabled the strain that lost its Carbazole-degrading ability to have overall higher fitness than the wild-type strain. These results suggest that the functions of the chromosomal genes contributed to the selection of plasmid derivatives with altered structures.

J Neurosci. 2009 Apr 8; 29(14): 4605-15
Kohutek ZA, diPierro CG, Redpath GT, Hussaini IM

MMPs (matrix metalloproteinases) and the related "a disintegrin and metalloproteinases" (ADAMs) promote tumorigenesis by cleaving extracellular matrix and protein substrates, including N-cadherin. Although N-cadherin is thought to regulate cell adhesion, migration, and invasion, its role has not been characterized in glioblastomas (GBMs). In this study, we investigated the expression and function of posttranslational N-cadherin cleavage in GBM cells as well as its regulation by protein kinase C (PKC). N-Cadherin cleavage occurred at a higher level in glioblastoma cells than in non-neoplastic astrocytes. Treatment with the PKC activator phorbol 12-myristate 13-acetate (PMA) increased N-cadherin cleavage, which was reduced by pharmacological inhibitors and short interfering RNA (siRNA) specific for ADAM-10 or PKC-alpha. Furthermore, treatment of GBM cells with PMA induced the translocation of ADAM-10 to the cell membrane, the site at which N-cadherin was cleaved, and this translocation was significantly reduced by the PKC-alpha inhibitor Gö6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrolo[3,4-c]Carbazole] or PKC-alpha short hairpin RNA. In functional studies, N-cadherin cleavage was required for GBM cell migration, as depletion of N-cadherin cleavage by N-cadherin siRNA, ADAM-10 siRNA, or a cleavage-site mutant N-cadherin, decreased GBM cell migration. Together, these results suggest that N-cadherin cleavage is regulated by a PKC-alpha-ADAM-10 cascade in GBM cells and may be involved in mediating GBM cell migration.

Chem Commun (Camb). 2009 Mar 28; 1464-6
Alayrac C, Schollmeyer D, Witulski B

The first total synthesis of the potent antioxidant antiostatin A1 is reported, where its key features rely on a chemo- and regioselective rhodium-catalysed crossed alkyne cyclotrimerisation reaction applying functionalised ynamides and a palladium-catalysed arylamidation reaction.

Biosci Biotechnol Biochem. 2009 Mar 23; 73(3): 744-6
Takahashi Y, Shintani M, Yamane H, Nojiri H

pCAR1 and pCAR2 are IncP-7 self-transmissible Carbazole degradative plasmids. Their respective hosts showed clearly different conjugative host ranges. Their complete nucleotide sequences were virtually the same, and can be regarded as structurally the same plasmid, indicating that the difference in the conjugative host range was caused by host cell backgrounds.

Curr Opin Chem Biol. 2009 Apr; 13(2): 152-60
Salas JA, Méndez C

The indoloCarbazoles constitute a family of natural products with potential therapeutic applications in the treatment of cancer and neurodegenerative disorders. Members of this family are either potent stabilizers of topoisomerase I-DNA covalent complex or potent inhibitors of protein kinases. Rebeccamycin, staurosporine, AT2433 and K252a are members of this family, which are produced by different actinomycete strains, and whose biosynthesis gene clusters have been isolated and characterized. A number of indoloCarbazole derivatives have been generated by applying combinatorial biosynthesis technologies to these clusters either in the producer strain or in the heterologous hosts after expression of part or the entire gene cluster. Combinatorial biosynthesis is therefore providing a new approach for increasing structural diversity in this family of natural products.

ACS Nano. 2008 Aug; 2(8): 1533-42
Kaewtong C, Jiang G, Felipe MJ, Pulpoka B, Advincula R

We report a detailed and quantitative study on the supramolecular complexation of amine-functionalized polyamidoamine (PAMAM) dendrimer G(4)-NH(2) with carboxylic acid terminal dendrons containing peripheral electroactive Carbazole groups of different generations (G(0)COOH, G(1)COOH, and G(2)COOH). While the focus is on a detailed understanding and mechanism of complex formation, subsequent electrochemical oxidation of the dendron surfmers resulted in the formation of nanoring structures electrodeposited on the conducting substrate. Complexation was confirmed by NMR, UV-vis, and IR measurements. Critical micelle concentration (CMC), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS) studies revealed that the ringlike structures were formed during the equilibrium-decomplexation stage and that the electrochemical process did not destroy the complex but rather stabilized it. The different generations of the dendrons provided various structures and complex formation efficacy. This type of template polymerization combined with electrochemically anodic oxidation has not been previously reported.