Characterization of an l-α,β-diaminopropionic acid polymer with comb-like structure isolated from a poly(ε-l-lysine)-producing Streptomyces sp.

First direct evidence for direct cell-membrane penetrations of polycationic homopoly(amino acid)s produced by bacteria

“…Although they are the first examples of bacterial PIECEs, further investigations of the cell-penetrating activities in bacterial polycationic isopeptides, such as γ-poly- l / d -diaminobutyric acid 4 , 5 , β-poly- l -diaminopropionic acid 6 , ε-poly- l -β-lysine 7 , cyanophycin 9 , 10 , and multi- l -diaminopropionyl-poly- l -diaminopropionic acid (Supplementary Fig. 1a ) 11 , would expand the potential applications of the CPP-driven technology.…”

“…To date, six polymers, ε-poly- l -α-lysine (ε-PαL, 1 ) 1 , 2 , ε-oligo- l -β-lysine (ε-OβL, 2 ) 3 , γ-poly- l / d -diaminobutyric acid 4 , 5 , β-poly- l -diaminopropionic acid 6 , ε-poly- l -β-lysine (our recent finding) 7 , and γ-poly- l / d -glutamic acid 1 , 8 have been identified. In addition to these linear polymers characterized by the isopeptide backbones, two branched polymers consisting of repeated dipeptide chains have also been found in bacteria: multi- l -arginyl-poly- l -aspartic acid (also referred to as cyanophycin) 9 , 10 and multi- l -diaminopropionyl-poly- l -diaminopropionic acid 11 . Among these eight homopoly(amino acid)s, γ-poly- l / d -glutamic acid is the only example of a naturally occurring polyanionic isopeptide.…”

Discovery of a Polyamino Acid Antibiotic Solely Comprising l-β-Lysine by Potential Producer Prioritization-Guided Genome Mining

“…14,15 Despite the considerable efforts since the discovery of poly-L-Lys, only four of its structural analogues have been described in the literature (Figure 1): γ-poly-L-diaminobutyric acid (poly-L-Dab) 16 and its mirror-image isomer γ-poly-D-diaminobutyric acid (poly-D-Dab), 17 β-poly-L-diaminopropionic acid (poly-l-Dap), 18 and the most recently discovered L-diaminopropionic acid homopolymer with an unusual branching comb-like structure [poly-di(L-Dap)]. 19 The fact that poly-L-Dab, poly-L-Dap, and poly-di(L-Dap), respectively, have been isolated from independent poly-L-Lys-producing Streptomyces species is particularly noteworthy. The above structural analogues were discovered using traditional microbial isolations from environmental flora, followed by time-consuming cultivation-based chemical screenings, 16−19 owing to the scarcity of biosynthetic knowledge that could allow genome mining-guided rational explorations.…”

“…Despite the considerable efforts since the discovery of poly- l -Lys, only four of its structural analogues have been described in the literature (Figure ): γ-poly- l -diaminobutyric acid (poly- l -Dab) and its mirror-image isomer γ-poly- d -diaminobutyric acid (poly- d -Dab), β-poly- l -diaminopropionic acid (poly-l-Dap), and the most recently discovered l -diaminopropionic acid homopolymer with an unusual branching comb-like structure [poly-di­( l -Dap)] . The fact that poly- l -Dab, poly- l -Dap, and poly-di­( l -Dap), respectively, have been isolated from independent poly- l -Lys-producing Streptomyces species is particularly noteworthy.…”

“…The above structural analogues were discovered using traditional microbial isolations from environmental flora, followed by time-consuming cultivation-based chemical screenings, − owing to the scarcity of biosynthetic knowledge that could allow genome mining-guided rational explorations. In 2008, we provided a breakthrough in addressing this obstructionnamely, we purified and identified an unusual enzyme responsible for the biosynthesis of poly- l -Lys .…”