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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.
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Considerations of the biosynthesis and molecular diversity of tolyporphins
Tolyporphins A–R constitute fundamentally distinct members of the tetrapyrrole pigments of life family. The 18 members present diversity at multiple levels including the chromophore (dioxobacteriochlorin, oxochlorin, porphyrin); composition of the pyrroline substituents (hydroxy, acetoxy, or one of four C -glycosides); and stereochemical configuration of the pyrroline substituents. Eleven of the 18 tolyporphins contain at least one C -glycoside; each C -glycoside has a β, d configuration and lacks a 6′-hydroxy group: 3′,6′-dideoxygalactose (common name abequose), 2′- O -acetyl-3′,6′-dideoxygalactose (2′- O -acetylabequose), 6′-deoxygalactose ( d -fucose), or 6′-deoxygulose (antiarose). Rare are such glycosides outside of tolyporphins: (2′- O -acetyl)abequose is reported only in the glycan polymer attached to the cell wall of two strains of Gram-negative bacteria, and antiarose is reported in one bacterial natural product and ∼50 plant cardiac glycosides. Eight of the 18 tolyporphins are bis( C -glycosides), an exceptionally uncommon motif in natural products. The biosynthetic pathways to the family of tolyporphins remain unknown. Regardless of such diversity, each tolyporphin member shares a common pattern of perimeter methyl substituents that coheres with derivation from uroporphyrinogen III, the universal precursor in the established pathway to native tetrapyrroles. Here, transformations required to convert uroporphyrinogen III to all 18 tolyporphins are considered in the context of plausible biosynthetic pathways. Heme d 1 , perhaps the closest relative (yet still a distant cousin) of tolyporphins, and for which key biosynthetic transformations remain undeciphered, provides a point of reference. Taken together, the work provides the foundation for bioinformatic searching for enzymes associated with the biosynthesis and diversification of tolyporphins.
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- Award ID(s):
- 1760839
- PAR ID:
- 10285891
- Date Published:
- Journal Name:
- New Journal of Chemistry
- Volume:
- 45
- Issue:
- 27
- ISSN:
- 1144-0546
- Page Range / eLocation ID:
- 12097 to 12107
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d1nj01761f
