Doubly Homologated Tyrosine-Containing Peptides from\nthe Cyanobacterium <i>Microcystis aeruginosa</i> NIES-4285\nand Their Biosynthesis

Chemical\ninvestigation of the cyanobacterium <i>Microcystis\naeruginosa</i> NIES-4285 led to the isolation of six new natural\nproducts, microginins 705 (<b>1</b>), 719 (<b>2</b>),\n733A (<b>3</b>), 733B (<b>4</b>), and 733C (<b>5</b>), and anabaenopeptin 885 (<b>7</b>), and three known compounds,\nanabaenopeptins 871 (<b>6</b>), B (<b>8</b>), and F (<b>9</b>). Planar structures and absolute configurations for <b>1</b>–<b>7</b> were determined by 2D NMR, HRMS, and\nMarfey’s analyses. Microginin 733C (<b>5</b>), and anabaenopeptins\n871 (<b>6</b>) and 885 (<b>7</b>) contained a unique residue\nof 2-amino-5-(4-hydroxyphenyl)pentanoic acid (Ahppa): doubly homologated\ntyrosine (di-hTyr). The biosynthetic origin of this nonproteinogenic\namino acid di-hTyr was investigated, and it was found that MaHphABCDE\nare involved in the production of di-hTyr. In addition, biochemical\ncharacterization of aminotransferase MaHphE showed that it is a promiscuous\nenzyme. This result expanded the biocatalytic toolbox for amino acid\nhomologation.