Novel Glycerophospholipid, Lipo- and N-acyl Amino Acids from Bacteroidetes: Isolation, Structure Elucidation and Bioactivity

Abstract

The 'core' metabolome of the Bacteroidetes genus <i>Chitinophaga</i> was recently discovered to consist of only seven metabolites. A structural relationship in terms of shared lipid moieties among four of them was postulated. Here, structure elucidation and characterization via ultra-high resolution mass spectrometry (UHR-MS) and nuclear magnetic resonance (NMR) spectroscopy of those four lipids (two lipoamino acids (LAAs), two lysophosphatidylethanolamines (LPEs)), as well as several other undescribed LAAs and <i>N</i>-acyl amino acids (NAAAs), identified during isolation were carried out. The LAAs represent closely related analogs of the literature-known LAAs, such as the glycine-serine dipeptide lipids 430 (<b>2</b>) and 654. Most of the here characterized LAAs (<b>1</b>, <b>5</b>-<b>11</b>) are members of a so far undescribed glycine-serine-ornithine tripeptide lipid family. Moreover, this study reports three novel NAAAs (<i>N</i>-(5-methyl)hexanoyl tyrosine (<b>14</b>) and <i>N</i>-(7-methyl)octanoyl tyrosine (<b>15</b>) or phenylalanine (<b>16</b>)) from <i>Olivibacter</i> sp. FHG000416, another Bacteroidetes strain initially selected as best in-house producer for isolation of lipid 430. Antimicrobial profiling revealed most isolated LAAs (<b>1</b>-<b>3</b>) and the two LPE 'core' metabolites (<b>12</b>, <b>13</b>) active against the Gram-negative pathogen <i>M. catarrhalis</i> ATCC 25238 and the Gram-positive bacterium <i>M. luteus</i> DSM 20030. For LAA <b>1</b>, additional growth inhibition activity against <i>B. subtilis</i> DSM 10 was observed.