Tistrellabactins A and B Are Photoreactive <i>C</i>‑Diazeniumdiolate Siderophores from the Marine-Derived Strain <i>Tistrella mobilis</i> KA081020-065

The C-diazeniumdiolate group in the amino acid graminine is emerging as a new microbially produced Fe(III) coordinating ligand in siderophores, which is photoreactive. While the few siderophores reported from this class have only been isolated from soil-associated microbes, here we report the first C-diazeniumdiolate siderophores tistrellabactins A and B, isolated from the bioactive marine-derived strain Tistrella mobilis KA081020-065. The structural characterization of the tistrellabactins reveals unique biosynthetic features including an NRPS module iteratively loading glutamine residues and a promiscuous adenylation domain yielding either tistrellabactin A with an asparagine residue or tistrellabactin B with an aspartic acid residue at analogous positions. Beyond the function of scavenging Fe(III) for growth, these siderophores are photoreactive upon irradiation with UV light, releasing the equivalent of nitric oxide (NO) and an H atom from the C-diazeniumdiolate group. Fe(III)-tistrellabactin is also photoreactive, with both the C-diazeniumdiolate and the β-hydroxyaspartate residues undergoing photoreactions, resulting in a photoproduct without the ability to chelate Fe(III)

<i>C</i>‑Diazeniumdiolate Graminine in the Siderophore Gramibactin Is Photoreactive and Originates from Arginine

Siderophores are synthesized by microbes to facilitate iron acquisition required for growth. Catecholate, hydroxamate, and α-hydroxycarboxylate groups comprise well-established ligands coordinating Fe(III) in siderophores. Recently, a C-type diazeniumdiolate ligand in the newly identified amino acid graminine (Gra) was found in the siderophore gramibactin (Gbt) produced by Paraburkholderia graminis DSM 17151. The N–N bond in the diazeniumdiolate is a distinguishing feature of Gra, yet the origin and reactivity of this C-type diazeniumdiolate group has remained elusive until now. Here, we identify l-arginine as the direct precursor to l-Gra through the isotopic labeling of l-Arg, l-ornithine, and l-citrulline. Furthermore, these isotopic labeling studies establish that the N–N bond in Gra must be formed between the Nδ and Nω of the guanidinium group in l-Arg. We also show the diazeniumdiolate groups in apo-Gbt are photoreactive, with loss of nitric oxide (NO) and H+ from each d-Gra yielding E/Z oxime isomers in the photoproduct. With the loss of Gbt’s ability to chelate Fe(III) upon exposure to UV light, our results hint at this siderophore playing a larger ecological role. Not only are NO and oximes important in plant biology for communication and defense, but so too are NO-releasing compounds and oximes attractive in medicinal applications

Image_1_Temporal Trends of Persistent Organic Pollutants in Sarasota Bay Common Bottlenose Dolphins (Tursiops truncatus).jpg

Legacy persistent organic pollutants (POPs) were measured in blubber samples collected from 196 common bottlenose dolphins (Tursiops truncatus) from 2000 to 2016 in the Sarasota Bay, Florida, ecosystem. Legacy POPs included polychlorinated biphenyl congeners (ΣPCB; sum of 37 congeners or congener groups), dichloro-diphenyl-trichloroethane (DDT) and transformation products (ΣDDT), chlordane and related compounds (ΣChlor), mirex, polybrominated diphenyl ether congeners (ΣPBDE, sum of five congeners), dieldrin and hexachlorobenzene (HCB). All POP compounds or compound groups declined in dolphin blubber over the study period. POP classes declined at different rates within classifications (sex, adult or calf). For example, dieldrin decline in male dolphins was greatest (−13% per year) while HCB decline was lower (−6.3% per year). For individual POP classes, rates of decline depended on classification. For example, ΣPCB, the POP class present at the highest concentration relative to other POPs, declined at −8.4, −7.8, and −5.6% per year in adult females, adult males and calves, respectively. Overall POP declines were highest in adult males and lowest in calves. Declines in POP concentration with time based on individual dolphins resampled at different time points were consistent with declines calculated based on yearly or biennial cross-sections taken from 2000 through 2016. Overall rates of decline in Sarasota Bay bottlenose dolphins were like declines seen for Great Lakes fish and about twice the rate of decline observed in arctic temporal trend data sets. POP trends appear to have leveled off since 2009 in Sarasota Bay dolphins. For example, ΣPCBs in calves appear to have stabilized at 21 mg/kg lipid. Recent published work on delphinids with blubber concentrations spanning those observed in the present work suggest that levels of legacy POPs currently observed in Sarasota dolphins may suppress population growth. Results from this study confirm the need for continued monitoring of POPs in the Sarasota Bay bottlenose dolphin population to see if concentrations are continuing to fall or have indeed plateaued.</p

Image_2_Temporal Trends of Persistent Organic Pollutants in Sarasota Bay Common Bottlenose Dolphins (Tursiops truncatus).jpg

Legacy persistent organic pollutants (POPs) were measured in blubber samples collected from 196 common bottlenose dolphins (Tursiops truncatus) from 2000 to 2016 in the Sarasota Bay, Florida, ecosystem. Legacy POPs included polychlorinated biphenyl congeners (ΣPCB; sum of 37 congeners or congener groups), dichloro-diphenyl-trichloroethane (DDT) and transformation products (ΣDDT), chlordane and related compounds (ΣChlor), mirex, polybrominated diphenyl ether congeners (ΣPBDE, sum of five congeners), dieldrin and hexachlorobenzene (HCB). All POP compounds or compound groups declined in dolphin blubber over the study period. POP classes declined at different rates within classifications (sex, adult or calf). For example, dieldrin decline in male dolphins was greatest (−13% per year) while HCB decline was lower (−6.3% per year). For individual POP classes, rates of decline depended on classification. For example, ΣPCB, the POP class present at the highest concentration relative to other POPs, declined at −8.4, −7.8, and −5.6% per year in adult females, adult males and calves, respectively. Overall POP declines were highest in adult males and lowest in calves. Declines in POP concentration with time based on individual dolphins resampled at different time points were consistent with declines calculated based on yearly or biennial cross-sections taken from 2000 through 2016. Overall rates of decline in Sarasota Bay bottlenose dolphins were like declines seen for Great Lakes fish and about twice the rate of decline observed in arctic temporal trend data sets. POP trends appear to have leveled off since 2009 in Sarasota Bay dolphins. For example, ΣPCBs in calves appear to have stabilized at 21 mg/kg lipid. Recent published work on delphinids with blubber concentrations spanning those observed in the present work suggest that levels of legacy POPs currently observed in Sarasota dolphins may suppress population growth. Results from this study confirm the need for continued monitoring of POPs in the Sarasota Bay bottlenose dolphin population to see if concentrations are continuing to fall or have indeed plateaued.</p

Identification of Portimine B, a New Cell Permeable Spiroimine That Induces Apoptosis in Oral Squamous Cell Carcinoma

Spiroimines are a class of compounds produced by marine dinoflagellates with a wide range of toxicity and therapeutic potential. The smallest of the cyclic imines, portimine, is far less toxic than other known members in several animal models. Portimine has also been shown to induce apoptosis and reduce the growth of a variety of cancer cell lines at low nanomolar concentrations. In an effort to discover new spiroimines, the current study undertook a metabolomic analysis of cultures of cyclic imine-producing dinoflagellates, and a new analog of portimine was discovered in which the five-membered cyclic ether is open. Further scrutiny with human oral cavity squamous cell carcinoma (OCSCC) cell lines revealed that the open ring congener was less potent than portimine A but could still lead to the accumulation of apoptotic gene transcripts, fragment genomic DNA, and reduce cancer cell proliferation in the range of 100–200 nM

Table_1_Temporal Trends of Persistent Organic Pollutants in Sarasota Bay Common Bottlenose Dolphins (Tursiops truncatus).DOCX

Legacy persistent organic pollutants (POPs) were measured in blubber samples collected from 196 common bottlenose dolphins (Tursiops truncatus) from 2000 to 2016 in the Sarasota Bay, Florida, ecosystem. Legacy POPs included polychlorinated biphenyl congeners (ΣPCB; sum of 37 congeners or congener groups), dichloro-diphenyl-trichloroethane (DDT) and transformation products (ΣDDT), chlordane and related compounds (ΣChlor), mirex, polybrominated diphenyl ether congeners (ΣPBDE, sum of five congeners), dieldrin and hexachlorobenzene (HCB). All POP compounds or compound groups declined in dolphin blubber over the study period. POP classes declined at different rates within classifications (sex, adult or calf). For example, dieldrin decline in male dolphins was greatest (−13% per year) while HCB decline was lower (−6.3% per year). For individual POP classes, rates of decline depended on classification. For example, ΣPCB, the POP class present at the highest concentration relative to other POPs, declined at −8.4, −7.8, and −5.6% per year in adult females, adult males and calves, respectively. Overall POP declines were highest in adult males and lowest in calves. Declines in POP concentration with time based on individual dolphins resampled at different time points were consistent with declines calculated based on yearly or biennial cross-sections taken from 2000 through 2016. Overall rates of decline in Sarasota Bay bottlenose dolphins were like declines seen for Great Lakes fish and about twice the rate of decline observed in arctic temporal trend data sets. POP trends appear to have leveled off since 2009 in Sarasota Bay dolphins. For example, ΣPCBs in calves appear to have stabilized at 21 mg/kg lipid. Recent published work on delphinids with blubber concentrations spanning those observed in the present work suggest that levels of legacy POPs currently observed in Sarasota dolphins may suppress population growth. Results from this study confirm the need for continued monitoring of POPs in the Sarasota Bay bottlenose dolphin population to see if concentrations are continuing to fall or have indeed plateaued.</p