@misc{nguyen_zhang_liu_zhang_jin_taniguchi_miller_lindsey_2023, title={Tolyporphins-Exotic Tetrapyrrole Pigments in a Cyanobacterium-A Review}, volume={28}, ISSN={["1420-3049"]}, url={https://doi.org/10.3390/molecules28166132}, DOI={10.3390/molecules28166132}, abstractNote={Tolyporphins were discovered some 30 years ago as part of a global search for antineoplastic compounds from cyanobacteria. To date, the culture HT-58-2, comprised of a cyanobacterium–microbial consortium, is the sole known producer of tolyporphins. Eighteen tolyporphins are now known—each is a free base tetrapyrrole macrocycle with a dioxobacteriochlorin (14), oxochlorin (3), or porphyrin (1) chromophore. Each compound displays two, three, or four open β-pyrrole positions and two, one, or zero appended C-glycoside (or –OH or –OAc) groups, respectively; the appended groups form part of a geminal disubstitution motif flanking the oxo moiety in the pyrroline ring. The distinct structures and repertoire of tolyporphins stand alone in the large pigments-of-life family. Efforts to understand the cyanobacterial origin, biosynthetic pathways, structural diversity, physiological roles, and potential pharmacological properties of tolyporphins have attracted a broad spectrum of researchers from diverse scientific areas. The identification of putative biosynthetic gene clusters in the HT-58-2 cyanobacterial genome and accompanying studies suggest a new biosynthetic paradigm in the tetrapyrrole arena. The present review provides a comprehensive treatment of the rich science concerning tolyporphins.}, number={16}, journal={MOLECULES}, author={Nguyen, Kathy-Uyen and Zhang, Yunlong and Liu, Qihui and Zhang, Ran and Jin, Xiaohe and Taniguchi, Masahiko and Miller, Eric S. and Lindsey, Jonathan S.}, year={2023}, month={Aug} }
 @article{wu_dou_nguyen_eppley_siwawannapong_zhang_lindsey_2022, title={Tailoring the AIE Chromogen 2-(2-Hydroxyphenyl)benzothiazole for Use in Enzyme-Triggered Molecular Brachytherapy}, volume={27}, ISSN={["1420-3049"]}, DOI={10.3390/molecules27248682}, abstractNote={A targeted strategy for treating cancer is antibody-directed enzyme prodrug therapy, where the enzyme attached to the antibody causes conversion of an inactive small-molecule prodrug into an active drug. A limitation may be the diffusion of the active drug away from the antibody target site. A related strategy with radiotherapeutics entails enzymatically promoted conversion of a soluble to insoluble radiotherapeutic agent, thereby immobilizing the latter at the target site. Such a molecular brachytherapy has been scarcely investigated. In distinct research, the advent of molecular designs for aggregation-induced emission (AIE) suggests translational use in molecular brachytherapy. Here, several 2-(2-hydroxyphenyl)benzothiazole substrates that readily aggregate in aqueous solution (and afford AIE) were elaborated in this regard. In particular, (1) the 2-(2-hydroxyphenyl) unit was derivatized to bear a pegylated phosphodiester that imparts water solubility yet undergoes enzymatic cleavage, and (2) a p-phenol unit was attached to the benzo moiety to provide a reactive site for final-step iodination (here examined with natural abundance iodide). The pegylated phosphodiester-iodinated benzothiazole undergoes conversion from aqueous-soluble to aqueous-insoluble upon treatment with a phosphatase or phosphodiesterase. The aggregation is essential to molecular brachytherapy, whereas the induced emission of AIE is not essential but provides a convenient basis for research development. Altogether, 21 compounds were synthesized (18 new, 3 known via new routes). Taken together, blending biomedical strategies of enzyme prodrug therapy with materials chemistry concerning substances that undergo AIE may comprise a step forward on the long road toward molecular brachytherapy.}, number={24}, journal={MOLECULES}, author={Wu, Zhiyuan and Dou, Jinghuai and Nguyen, Kathy-Uyen and Eppley, Jayden C. and Siwawannapong, Kittipan and Zhang, Yunlong and Lindsey, Jonathan S.}, year={2022}, month={Dec} }
 @article{jin_zhang_zhang_nguyen_lindsey_miller_2021, title={Identification of Putative Biosynthetic Gene Clusters for Tolyporphins in Multiple Filamentous Cyanobacteria}, volume={11}, ISSN={["2075-1729"]}, DOI={10.3390/life11080758}, abstractNote={Tolyporphins A–R are unusual tetrapyrrole macrocycles produced by the non-axenic filamentous cyanobacterium HT-58-2. A putative biosynthetic gene cluster for biosynthesis of tolyporphins (here termed BGC-1) was previously identified in the genome of HT-58-2. Here, homology searching of BGC-1 in HT-58-2 led to identification of similar BGCs in seven other filamentous cyanobacteria, including strains Nostoc sp. 106C, Nostoc sp. RF31YmG, Nostoc sp. FACHB-892, Brasilonema octagenarum UFV-OR1, Brasilonema octagenarum UFV-E1, Brasilonema sennae CENA114 and Oculatella sp. LEGE 06141, suggesting their potential for tolyporphins production. A similar gene cluster (BGC-2) also was identified unexpectedly in HT-58-2. Tolyporphins BGCs were not identified in unicellular cyanobacteria. Phylogenetic analysis based on 16S rRNA and a common component of the BGCs, TolD, points to a close evolutionary history between each strain and their respective tolyporphins BGC. Though identified with putative tolyporphins BGCs, examination of pigments extracted from three cyanobacteria has not revealed the presence of tolyporphins. Overall, the identification of BGCs and potential producers of tolyporphins presents a collection of candidate cyanobacteria for genetic and biochemical analysis pertaining to these unusual tetrapyrrole macrocycles.}, number={8}, journal={LIFE-BASEL}, author={Jin, Xiaohe and Zhang, Yunlong and Zhang, Ran and Nguyen, Kathy-Uyen and Lindsey, Jonathan S. and Miller, Eric S.}, year={2021}, month={Aug} }
 @article{fujita_zhang_wu_lindsey_2020, title={Chromogenic agents built around a multifunctional double-triazine framework for enzymatically triggered cross-linking under physiological conditions}, volume={44}, ISSN={["1369-9261"]}, DOI={10.1039/c9nj06187h}, abstractNote={A molecular architecture designed for bioconjugation and internal absorption ratiometry undergoes enzymatically triggered cleavage of glucosyl groups and subsequent oxidative dimerization in aqueous solution to yield indigoid-containing scaffolds.}, number={10}, journal={NEW JOURNAL OF CHEMISTRY}, author={Fujita, Hikaru and Zhang, Yunlong and Wu, Zhiyuan and Lindsey, Jonathan S.}, year={2020}, month={Mar}, pages={3856–3867} }
 @article{zhang_wu_takashima_nguyen_matsumoto_lindsey_2020, title={Engineering of an archaeal phosphodiesterase to trigger aggregation-induced emission (AIE) of synthetic substrates}, volume={44}, ISSN={["1369-9261"]}, DOI={10.1039/d0nj03208e}, abstractNote={Aggregation-induced emission (AIE) probes that can be triggered by enzymatic activity are valuable for applications across the life sciences.}, number={33}, journal={NEW JOURNAL OF CHEMISTRY}, author={Zhang, Yunlong and Wu, Zhiyuan and Takashima, Ippei and Nguyen, Kathy-Uyen and Matsumoto, Nobuyuki and Lindsey, Jonathan S.}, year={2020}, month={Sep}, pages={14266–14277} }
 @article{barnhart-dailey_zhang_zhang_anthony_aaron_miller_lindsey_timlin_2019, title={Cellular localization of tolyporphins, unusual tetrapyrroles, in a microbial photosynthetic community determined using hyperspectral confocal fluorescence microscopy}, volume={141}, ISSN={0166-8595 1573-5079}, url={http://dx.doi.org/10.1007/s11120-019-00625-w}, DOI={10.1007/s11120-019-00625-w}, abstractNote={The cyanobacterial culture HT-58-2, composed of a filamentous cyanobacterium and accompanying community bacteria, produces chlorophyll a as well as the tetrapyrrole macrocycles known as tolyporphins. Almost all known tolyporphins (A-M except K) contain a dioxobacteriochlorin chromophore and exhibit an absorption spectrum somewhat similar to that of chlorophyll a. Here, hyperspectral confocal fluorescence microscopy was employed to noninvasively probe the locale of tolyporphins within live cells under various growth conditions (media, illumination, culture age). Cultures grown in nitrate-depleted media (BG-11 0  vs. nitrate-rich, BG-11) are known to increase the production of tolyporphins by orders of magnitude (rivaling that of chlorophyll a) over a period of 30-45 days. Multivariate curve resolution (MCR) was applied to an image set containing images from each condition to obtain pure component spectra of the endogenous pigments. The relative abundances of these components were then calculated for individual pixels in each image in the entire set, and 3D-volume renderings were obtained. At 30 days in media with or without nitrate, the chlorophyll a and phycobilisomes (combined phycocyanin and phycobilin components) co-localize in the filament outer cytoplasmic region. Tolyporphins localize in a distinct peripheral pattern in cells grown in BG-11 0  versus a diffuse pattern (mimicking the chlorophyll a localization) upon growth in BG-11. In BG-11 0 , distinct puncta of tolyporphins were commonly found at the septa between cells and at the end of filaments. This work quantifies the relative abundance and envelope localization of tolyporphins in single cells, and illustrates the ability to identify novel tetrapyrroles in the presence of chlorophyll a in a photosynthetic microorganism within a non-axenic culture.}, number={3}, journal={Photosynthesis Research}, publisher={Springer Science and Business Media LLC}, author={Barnhart-Dailey, Meghan and Zhang, Yunlong and Zhang, Ran and Anthony, Stephen M. and Aaron, Jesse S. and Miller, Eric S. and Lindsey, Jonathan S. and Timlin, Jerilyn A.}, year={2019}, month={Mar}, pages={259–271} }
 @article{hughes_jin_zhang_zhang_tran_williams_lindsey_miller_2018, title={Genome sequence, metabolic properties and cyanobacterial attachment of Porphyrobacter sp. HT-58-2 isolated from a filamentous cyanobacterium–microbial consortium}, volume={164}, ISSN={1350-0872 1465-2080}, url={http://dx.doi.org/10.1099/mic.0.000706}, DOI={10.1099/mic.0.000706}, abstractNote={Tolyporphins are structurally diverse tetrapyrrole macrocycles produced by the cyanobacterial culture HT-58-2. Although tolyporphins were discovered over 25 years ago, little was known about the microbiology of the culture. The studies reported herein expand the description of the community of predominantly alphaproteobacteria associated with the filamentous HT-58-2 cyanobacterium and isolate a dominant bacterium, Porphyrobacter sp. HT-58-2, for which the complete genome is established and growth properties are examined. Fluorescence in situ hybridization (FISH) analysis of the cyanobacterium-microbial community with a probe targeting the 16S rRNA of Porphyrobacter sp. HT-58-2 showed fluorescence emanating from the cyanobacterial sheath. Although genes for the biosynthesis of bacteriochlorophyll a (BChl a) are present in the Porphyrobacter sp. HT-58-2 genome, the pigment was not detected under the conditions examined, implying the absence of phototrophic growth. Comparative analysis of four Porphyrobacter spp. genomes from worldwide collection sites showed significant collinear gene blocks, with two inversions and three deletion regions. Taken together, the results enrich our understanding of the HT-58-2 cyanobacterium-microbial culture.}, number={10}, journal={Microbiology}, publisher={Microbiology Society}, author={Hughes, Rebecca-Ayme and Jin, Xiaohe and Zhang, Yunlong and Zhang, Ran and Tran, Sabrina and Williams, Philip G. and Lindsey, Jonathan S. and Miller, Eric S.}, year={2018}, month={Oct}, pages={1229–1239} }
 @article{hughes_zhang_zhang_williams_lindsey_miller_2017, title={Genome Sequence and Composition of a Tolyporphin-Producing Cyanobacterium-Microbial Community}, volume={83}, ISSN={["1098-5336"]}, DOI={10.1128/aem.01068-17}, abstractNote={ABSTRACT}, number={19}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Hughes, Rebecca-Ayme and Zhang, Yunlong and Zhang, Ran and Williams, Philip G. and Lindsey, Jonathan S. and Miller, Eric S.}, year={2017}, month={Oct} }
 @article{zhang_zhang_nazari_bagley_miller_williams_muddiman_lindsey_2017, title={Mass spectrometric detection of chlorophyll a and the tetrapyrrole secondary metabolite tolyporphin A in the filamentous cyanobacterium HT-58-2. Approaches to high-throughput screening of intact cyanobacteria}, volume={21}, ISSN={["1099-1409"]}, DOI={10.1142/s108842461750078x}, abstractNote={ Tolyporphins are unusual tetrapyrrole macrocycles produced by the filamentous cyanobacterium–microbial community HT-58-2, the only known source to date. Numerous cyanobacterial samples have been collected worldwide but most have not been screened for secondary metabolites. Identification of tolyporphins typically has entailed lipophilic extraction followed by chromatographic fractionation and spectroscopic and/or mass spectrometric analysis. For quantitation, lengthy lipophilic extraction, sample processing and HPLC separation are needed. Examination by MALDI-TOF-MS (with the matrix 1,5-diaminonaphthalene) of lipophilic crude extracts of small-scale HT-58-2 samples (2 mL) without chromatographic fractionation enabled semi-quantitation of tolyporphin A over a 41-day growth period. Screening for tolyporphin A in intact or slightly sheared and vortexed HT-58-2 samples (no lipophilic extraction), and confirmation of identity by tandem MS, were carried out by IR-MALDESI-FTMS. Tolyporphin A was identified by the molecular ion and four characteristic fragments. The molecular ion of chlorophyll [Formula: see text] also was observed. The sheared and vortexed sample contained substantial numbers of intact cells as demonstrated by regrowth of the filamentous cyanobacterium–microbial culture. The semi-quantitative and rapid qualitative methods developed herein should facilitate examination of other tolyporphin-producing organisms among the vast worldwide strains of cyanobacteria as well as investigation of the biosynthesis of tolyporphins. }, number={11}, journal={JOURNAL OF PORPHYRINS AND PHTHALOCYANINES}, author={Zhang, Yunlong and Zhang, Ran and Nazari, Milad and Bagley, Michael C. and Miller, Eric S. and Williams, Philip G. and Muddiman, David C. and Lindsey, Jonathan S.}, year={2017}, month={Nov}, pages={759–768} }
 @article{zhang_zhang_hughes_dai_gurr_williams_miller_lindsey_2017, title={Quantitation of Tolyporphins, Diverse Tetrapyrrole Secondary Metabolites with Chlorophyll-Like Absorption, from a Filamentous Cyanobacterium-Microbial Community}, volume={29}, ISSN={0958-0344}, url={http://dx.doi.org/10.1002/pca.2735}, DOI={10.1002/pca.2735}, abstractNote={Abstract}, number={2}, journal={Phytochemical Analysis}, publisher={Wiley}, author={Zhang, Yunlong and Zhang, Ran and Hughes, Rebecca-Ayme and Dai, Jingqiu and Gurr, Joshua R. and Williams, Philip G. and Miller, Eric S. and Lindsey, Jonathan S.}, year={2017}, month={Nov}, pages={205–216} }