Albofungin and chloroalbofungin: antibiotic crystals with 2D but not 3D isostructurality

Abstract

The potent antibiotics albofungin [systematic name: (1S,4R,8aR)-13-amino-1,15,16-trihydroxy-4-methoxy-12-methyl-3,4,8a,13-tetrahydro-1H-xantheno[4′,3′,2′:4,5][1,3]benzodioxino[7,6-g]isoquinoline-14,17(2H,9H)-dione, C27H24N2O9, 1] and its chlorinated analogue chloroalbofungin (the 11-chloro analogue, C27H23ClN2O9, 2) have been crystallized following their isolation from the bacterial strain Streptomyces chrestomyceticus and their structures determined by single-crystal X-ray diffraction. The novel N-aminoquinolone molecular arrangement shows N—N bond lengths of 1.4202 (16) and 1.424 (2) Å in 1 and 2, respectively. The regiochemistry of chloro substitution in the A-ring is para to the quinolone O atom, with a C—Cl bond length of 1.741 (2) Å. The absolute stereochemistry at three chiral centres of the xanthone rings (i.e. 10S, 13R and 19R) is confirmed. Both compounds crystallize in chiral Sohncke space groups consistent with enantiopurity, but are not fully isostructural. A preserved supramolecular construct (SC) confers two-dimensional (2D) isostructurality, but the SC self-associates via either a twofold screw operation in 1, giving a monoclinic P21 structure, or a twofold rotation in 2, affording a monoclinic C2 structure with a doubled unit-cell axis.

Discovery, Yield Improvement, and Application in Marine Coatings of Potent Antifouling Compounds Albofungins Targeting Multiple Fouling Organisms

“…Albofungins were isolated and purified as previously described ( She et al, 2021 ). The purity of tested compounds was confirmed by high-performance liquid chromatography (95% purity, HPLC, Waters 2695, Milford, MA, United States), and their structures were determined by the Bruker NMR spectrometers (Bruker, Billerica, MA, United States) and X-ray crystallography as previously described ( Ye et al, 2020 ; She et al, 2021 ).…”

“…Albofungin and its derivatives were identified as secondary metabolites from various Streptomyces species, and they belong to polycyclic isoquinolone–xanthone family. Albofungin and chloroalbofungin have been crystallized and their structures were determined by single-crystal X-ray diffraction ( Ye et al, 2020 ). Our previous study has reported remarkable antibacterial activities against “ESKAPE pathogens” and antitumor activities of albofungin and its derivatives isolated from the bacterium S. chrestomyceticus BCC 24770 ( She et al, 2021 ).…”

Discovery, Bioactivity Evaluation, Biosynthetic Gene Cluster Identification, and Heterologous Expression of Novel Albofungin Derivatives

“…Given that they shared a similar biosynthesis pathway with 3 and 4, 1 and 2 might reasonably possess the same stereochemistry as 3 and 4. The absolute configurations of 3 and 4 were established as 10-S, 13-R, and 19-R by using the X-ray crystallographic analysis in our previous study (Ye et al, 2020). The circular dichroism experiment was conducted to verify the stereochemistry of 1 and 2.…”

Isolation, Biosynthesis, and Biological Activity of Polycyclic Xanthones From Actinomycetes

“…Streptomycetes are the most chemically studied actinobacteria and proven to have an extraordinary ability to produce colored polycyclic xanthones ( Winter et al, 2013 ). Currently, their fermentation broths were frequently extracted with an equal volume of ethyl acetate three times to obtain the crude extracts ( Hu et al, 2019 ; Xu et al, 2020 ; Ye et al, 2020 ; She et al, 2021 ). Further isolation and identification procedure might be hardly hindered by the low solubility of this kind of pigments in many organic solvents ( Nakagawa et al, 1986 ; Hu et al, 2020 ), and chemical modification by acetylation or methylation could be used as a solution to address this problem ( Ömura et al, 1986 ).…”