Response to RC2

Abstract

Interactive comment on "Multipoint Reconstruction of Wind Speeds" by Christian Behnken et al. Christian Behnken et al.

Biosynthesis and Chemical Applications of Thioamides

“…Manipulation of the regulatory elements involved in the global activation of secondary metabolism in R. cellulolyticum sustained the production of closthioamide and allowed isolation of seven congeners which showed varied levels of bioactivity. 40 Evaluation of the antibacterial activity of the congeners demonstrated the importance of all six thioamide moieties, terminal aromatic residues, the modular arrangement of the β-thioalanyl units, and the distinct length of spacer units for antibacterial activity. 40,41 Moreover, it was also found that closthioamide is a selective Cu(I) chelator akin to methanobactin and forms a compact symmetrical dinuclear copper complex.…”

“…40 Evaluation of the antibacterial activity of the congeners demonstrated the importance of all six thioamide moieties, terminal aromatic residues, the modular arrangement of the β-thioalanyl units, and the distinct length of spacer units for antibacterial activity. 40,41 Moreover, it was also found that closthioamide is a selective Cu(I) chelator akin to methanobactin and forms a compact symmetrical dinuclear copper complex. 13,42 Through synthesis and application of deuterium-and fluorine-labeled probes (see below), initial insights into closthioamide biosynthesis were obtained, which predicted the involvement of an unusual non-ribosomal peptide synthetase (NRPS).…”

“…13,42 Through synthesis and application of deuterium-and fluorine-labeled probes (see below), initial insights into closthioamide biosynthesis were obtained, which predicted the involvement of an unusual non-ribosomal peptide synthetase (NRPS). 21,40 A very recent study reported the closthioamide biosynthetic gene cluster (BGC) in R. cellulolyticum and demonstrated that closthioamide biosynthesis involves a novel thiotemplated peptide assembly line that differs from known NRPSs. 34,43 Extensive genome editing and isolation of intermediates from the knock out mutants revealed that the closthioamide BGC consisted of genes ctaA-M along ( Figure 3A) and a preliminary biosynthetic pathway has been proposed ( Figure 3B).…”

“…4041 First, closthioamide variants were prepared with some or all of the thioamides replaced by amides, variants which had been observed in R. cellulolyticum extracts. 40 Using these compounds, amide variants were not converted to thioamide variants, but that thioamide variants were hydrolyzed to form the amide variants. Thus, it appeared that thioamide incorporation occurred during closthioamide backbone synthesis, not through downstream modification of amides.…”