Paenimacrolidin, a novel macrolide antibiotic from Paenibacillus sp. F6-B70 active against methicillin-resistant Staphylococcus aureus.
Bottom Line: Elucidation of the structure by nuclear magnetic resonance and infrared spectroscopy revealed that the active compound, paenimacrolidin (PAM), was a novel 22-membered macrolide with side-chains.The antibiotic capacity of PAM was compromised by its instability, which can be overcome significantly with addition of an anti-oxidant.To our knowledge, this is the first report of the isolation of an active macrolide from paenibacilli, which may be a promising source of novel antibiotics.
Affiliation: Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China. email@example.comShow MeSH
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Mentions: For PKS, 22 independent clones were sequenced and only four different nucleotide sequences were obtained (Table 1). The deduced amino acid sequences of these four unique DNA fragments were highly related (72.6–77.7% identity) to known trans‐AT PKS sequences, suggesting that F6‐B70 hosts trans‐AT PKSs. To verify the structure of PKS in F6‐B70, the primers derived from two independent KS domains were used to amplify DNA fragments in between and a 4209 bp fragment was obtained. Sequence alignment with representative PKS clusters revealed that the fragment contains five domains, including two KS, one dehydratase (DH), one ketoreductase and one ACP (Fig. 2A) (Weber et al., 2008), confirming that strain F6‐B70 contains trans‐PKS. It has been reported that the ∼230‐amino‐acid internal region of KS domains generated by PCR was sufficient to provide structural information (Nguyen et al., 2008). We thus constructed a phylogenetic tree using a neighbour‐joining algorithm based on the unique PKS sequences of F6‐B70 and the closest homologues. As shown in Fig. 2B, all of these four KS sequences were clustered into trans‐AT PKSs clades, indicating that F6‐B70 hosts trans‐AT PKSs. Three KS sequences, PKSI‐3, PKSI‐4 and PKSI‐5, belong to clade I, implicating a branched substrate. On the contrary, PKSI‐2 was grouped into the single‐bond subclade of clade V, suggesting that the substrate may contain a single bond between two specific carbons.
Affiliation: Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China. firstname.lastname@example.org