Genomics-driven discovery of chiral triscatechol siderophores with enantiomeric Fe(iii) coordination

Abstract

Synthesis and genome mining leverage access to diastereomers of the siderophore cyclic trichrysobactin. Computational modeling and CD spectroscopy address effects that ligand-based stereochemistry exerts on the configuration at Fe(iii).

Ruckerbactin Produced by Yersinia ruckeri YRB Is a Diastereomer of the Siderophore Trivanchrobactin Produced by Vibrio campbellii DS40M4

“…13 HPLC separation of the FDAAderivatized amino acids in the presence of added FDAAderivatized standards of L Arg, D Arg, L Ser, and D Ser established the presence of L Arg and L Ser in 1−3 (Figure S28). Thus, the chiral amino acid analysis confirmed the genomic prediction of L Ser and L Arg in ruckerbactin, (DHB L Arg L Ser) 3 , making it the diastereomeric counter to trivanchrobactin, (DHB D Arg L Ser) 3 .…”

“…2,3 The BGCs for frederiksenibactin in Y. f rederiksenii ATCC 3364 and CTC in D. chrysanthemi EC16 are also consistent with the presence of L Lys and D Lys, respectively, with the presence of an epimerase in the BGC in D. chrysanthemi EC16. 3 Moreover the chirality at the Fe(III) site for Fe(III)−frederiksenibactin, Δ, and Fe(III)−CTC, Λ, matches the chirality of Fe(III) coordination by ruckerbactin, Δ, and trivanchrobactin, Λ. Further investigations into the effect of chirality at the Fe(III) site of ruckerbactin and trivanchrobactin on iron uptake and utilization are in progress.…”

“…The question arises whether L Arg in ruckerbactin sets the chirality at the Fe(III) site in Fe(III)−ruckerbactin in the same manner that L Lys directs formation of the Δ configuration in Fe(III)−frederiksenibactin. 3 In an octahedral metal complex, tris bidentate catechol coordination may result in either the Δ or Λ configuration (not taking into account the meridional and facial geometries imposed by the asymmetry of 2,3-DHBA). Enterobactin (5), the macrolactone of (DHB L Ser) 3 , and its synthetic enantiomer, the macrolactone of (DHB D Ser) 3 , adopt the Δ and Λ configurations, respectively, on coordination of Fe(III), 14,15 demonstrating the influence of D-and L-Ser on the chirality of the Fe(III) complex.…”

“…Recently the tris catechol siderophore frederiksenibactin was reported from Yersinia f rederiksenii ATCC 3364, which is the oligoserine (DHB L Lys L Ser) 3 . Fe(III)−frederiksenibactin, like Fe(III)−ruckerbactin, adopts the Δ configuration at the Fe(III) site, 3 as a result of the presence of L Lys. While the true diastereomer of frederiksenibactin is not known, the macrolactone of (DHB D Lys L Ser) 3 is the siderophore cyclic trichrysobactin (CTC) produced by the plant pathogen Dickeya chrysanthemi EC16.…”

“…The archetypic siderophore enterobactin (5), produced by many enteric and pathogenic microbes, is a triscatecholamide siderophore framed on a cyclic macrolactone backbone of L Ser in which each Ser amine is appended by the catechol 2,3-dihydroxybenzoate (DHB). Nature has capitalized on the oligo-L Ser core as observed for example in trivanchrobactin ( 6), 1 cyclic trichrysobactin (7), 2 frederiksenibactin (8), 3 and the oligo L Thr core as observed for example in bacillibactin (9). 4 With the exception of enterobactin, the other serine-based tris catechol siderophores are distinguished by the presence of an amino acid spacer between L Ser and 2,3-DHBA.…”