| Autor: |
Kudo F; Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 152-8551, Japan., Chikuma T; Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 152-8551, Japan., Nambu M; Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 152-8551, Japan., Chisuga T; Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 152-8551, Japan., Sumimoto S; Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan., Iwasaki A; Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan., Suenaga K; Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan., Miyanaga A; Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 152-8551, Japan., Eguchi T; Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 152-8551, Japan. |
| Abstrakt: |
Lyngbyapeptin B is a hybrid polyketide-nonribosomal peptide isolated from particular marine cyanobacteria. In this report, we carried out genome sequence analysis of a producer cyanobacterium Moorena bouillonii to understand the biosynthetic mechanisms that generate the unique structural features of lyngbyapeptin B, including the ( E )-3-methoxy-2-butenoyl starter unit and the C-terminal thiazole moiety. We identified a putative lyngbyapeptin B biosynthetic ( lynB ) gene cluster comprising nine open reading frames that include two polyketide synthases (PKSs: LynB1 and LynB2), four nonribosomal peptide synthetases (NRPSs: LynB3, LynB4, LynB5, and LynB6), a putative nonheme diiron oxygenase (LynB7), a type II thioesterase (LynB8), and a hypothetical protein (LynB9). In vitro enzymatic analysis of LynB2 with methyltransferase (MT) and acyl carrier protein (ACP) domains revealed that the LynB2 MT domain (LynB2-MT) catalyzes O-methylation of the acetoacetyl-LynB2 ACP domain (LynB2-ACP) to yield ( E )-3-methoxy-2-butenoyl-LynB2-ACP. In addition, in vitro enzymatic analysis of LynB7 revealed that LynB7 catalyzes the oxidative decarboxylation of (4 R )-2-methyl-2-thiazoline-4-carboxylic acid to yield 2-methylthiazole in the presence of Fe 2+ and molecular oxygen. This result indicates that LynB7 is responsible for the last post-NRPS modification to give the C-terminal thiazole moiety in lyngbyapeptin B biosynthesis. Overall, we identified and characterized a new marine cyanobacterial hybrid PKS-NRPS biosynthetic gene cluster for lyngbyapeptin B production, revealing two unique enzymatic logics. |
