“…The observed decompositions of ions [BV+H] + and [BV−H] − in Fig. 4 are in good agreement with decomposition of this ions described elsewhere [ 15 ]. Fig.…”
A commercially available biliverdin sample was analyzed by means of HPLC/ESI–MS and NMR spectroscopy. It was been found that beside the main IXα 5Z,10Z,15Z isomer, the sample contains also the geometric isomer IXα 5Z,10Z,15E. It was also found the isomers behave differentially upon “in-source” fragmentation in negative ion mode (in contrast to the their behavior upon “in-source” fragmentation in positive ion mode and to their behavior upon MS/MS fragmentation in both modes): the relative abundances of deprotonated molecules and fragment ions are significantly different for both isomers, which can be used as an analytical tool to differentiate between the isomers.Graphical abstract
Electronic supplementary materialThe online version of this article (10.1007/s00706-018-2161-7) contains supplementary material, which is available to authorized users.
“…The observed decompositions of ions [BV+H] + and [BV−H] − in Fig. 4 are in good agreement with decomposition of this ions described elsewhere [ 15 ]. Fig.…”
A commercially available biliverdin sample was analyzed by means of HPLC/ESI–MS and NMR spectroscopy. It was been found that beside the main IXα 5Z,10Z,15Z isomer, the sample contains also the geometric isomer IXα 5Z,10Z,15E. It was also found the isomers behave differentially upon “in-source” fragmentation in negative ion mode (in contrast to the their behavior upon “in-source” fragmentation in positive ion mode and to their behavior upon MS/MS fragmentation in both modes): the relative abundances of deprotonated molecules and fragment ions are significantly different for both isomers, which can be used as an analytical tool to differentiate between the isomers.Graphical abstract
Electronic supplementary materialThe online version of this article (10.1007/s00706-018-2161-7) contains supplementary material, which is available to authorized users.
“…intestinal sulfonation of gambogic acid in the rat) and the subsequent neutral loss of H 2 SO 3 in negative ion mode for both ESI and CID of the sulfonated compound during MS/MS analysis 9 . The 581.242 m/z ion observed in both 1 [M-H] − and 2 [M-H-H 2 SO 3 ] − both follow similar CID for BV as previously described in the literature 10 . Interestingly, the CID spectra for 1 and 2 also feature a 285.126 m/z ion as a prominent fragment, and this fragment has been reported in the literature as a prominent fragment for UCB under similar CID conditions 11 indicating that all 3 compounds have this dipyrrole moiety in common (Fig.…”
Biliverdin (BV) possesses antioxidant and anti-inflammatory properties, with previous reports identifying protection against oxidant and inflammatory injury in animal models. Recent reports indicate that intra-duodenal administration of BV results in the formation of an uncharacterised metabolite, which is potently absorbed into the blood and excreted into the bile. This compound may be responsible for protection against inflammatory responses. This study aimed to identify novel, enterally-derived BV metabolites and determine the source of their metabolic transformation. Rat duodena and bacterial cultures of
Citrobacter youngae
were treated with BV and subsequently analysed via high performance liquid chromatography/high resolution tandem mass spectrometry to identify and characterise metabolites of BV. A highly abundant metabolite was detected in duodenal wash and bacterial culture supernatants with a 663.215 m/z (3 ppm mass accuracy) and a composition of C
33
N
4
O
9
H
36
S, which conformed to the predicted structure of bilirubin-10-sulfonate (BRS) and possessed a λ
max
of 440 nm. Bilirubin-10-sulfonate was then synthesized for comparative LCMS/MS analysis and matched with that of the biologically formed BV metabolite. This report confirms the formation of a previously undocumented metabolite of BV in mammals, indicating that a new metabolic pathway likely exists for BV metabolism requiring enteric bacteria,
Citrobacter youngae
. These data may have important implications with regard to understanding and harnessing the therapeutic efficacy of oral BV administration.
“…These compounds were found in the crude extracts of multiple native producing strains and heterologous expression strains, suggesting they are common metabolites among actinomycetes; however, we could not link their presence to any secondary metabolite BGCs. After further investigation using HRESIMS/MS, it was confirmed that they are two known primary metabolites, biliverdin 157 and coproporphyrin III 158 One hypothesis is that actinomycetes utilised the heme related metabolites to chelate metals presented in the environment to improve their resistance. 161 The tree and KEGG orthology information was reproduced from Annotree 160 .…”
Section: Primary Metabolisms Of the Actinobacteria Assemblages In New...mentioning
<p><b>Microbial secondary metabolites have made a remarkable contribution to the therapeutics on the market today, particularly in the development of new antimicrobials. The majority of currently employed antimicrobial drugs are either directly biosynthesised by microorganisms or based on the structures of microbial metabolites. The discovery of the antibiotic penicillin in 1928 launched the golden age of antimicrobials. Since that time, bioactive natural products have helped us double our lifespans. They have greatly reduced the mortality and morbidity associated with infectious diseases and revolutionised the pharmaceutical industry. Unfortunately, the introduction of novel antimicrobial drugs into clinical practice has almost always led to resistance to those drugs, which dramatically decreases the useful lifespans of the drugs. </b></p>
<p>To address this challenge, researchers began to explore new sources for natural product screening, from the traditional phenotypic screening of soil samples to other ecological niches. The microbial assemblages in lichens have become increasingly recognised as an underestimated repertoire of bioactive compounds. This study examined the biosynthetic and chemical diversity of actinobacteria isolated from New Zealand lichen samples using ‘dry lab’ and ‘wet lab’ approaches. </p>
<p>More than 500 actinobacteria were isolated during the course of this study, and an in-house high-throughput NGS library preparation platform was developed to sequence these isolates. Multidimensional analyses were then conducted to explore the phylogenetic and functional divergence in our sequencing datasets. Eight biosynthetic pathways mined from our datasets were cloned and/or refactored. These constructs were then transferred to different heterologous expression hosts and screened for the production of new metabolites using a python-assisted GNPS (Global Natural Product Social Molecular Networking) platform that was developed as part of this work. Four heterologous expression systems were identified as good leads and subjected to further study, leading to the identification and characterisation of chemical entities that have not previously been reported. This thesis validated that the New Zealand lichens are a novel genetic and chemical reservoir for natural product biosynthesis study. Analysis of over 300 genomes reconstructed from lichen sourced isolates uncovered the phylogenetic divergence and function novelty, shed light on biosynthetic dark matter, and provided a promising direction for future study.</p>
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