Genome Mining Discovery of a New Benzazepine Alkaloid Pseudofisnin A from the Marine Fungus <i>Neosartorya pseudofischeri</i> F27-1

• Автори: Xiao-Xin Xue (Автор), Lin Chen (Автор), Man-Cheng Tang (Автор)
• Формат: Книга
• Опубліковано: MDPI AG, 2022-10-01T00:00:00Z.
• Предмети: article
• Онлайн доступ: Connect to this object online.
• Notes: 10.3390/antibiotics11101444; 2079-6382
• Keywords: 1-benzazepine; <span style="font-variant: small-caps">l</span>-kynurenine; genome mining; biosynthesis; iterative methyltransferase; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 11, Iss 10, p 1444 (2022)

<span style="font-variant: small-caps;">l</span>-Kynurenine (Kyn) is an intermediate in the kynurenine pathway and is also found to be a building block or biosynthetic precursor to bioactive natural products. Recent studies revealed that <span style="font-variant: small-caps;">l</span>-Kyn can be incorporated via nonribosomal peptide synthetase (NRPS) biosynthetic routes to generate 1-benzazepine-containing compounds, while 1-benzazepine is a pharmaceutically important scaffold that is rarely found in natural products. Using a core biosynthetic enzyme-guided genome-mining approach, we discovered a biosynthetic gene cluster from <i>Neosartorya pseudofischeri</i> and identified that it encodes for the biosynthesis of pseudofisnins, novel 1-benzazepine-containing compounds. The biosynthetic pathway of pseudofisnins was elucidated through in vivo and in vitro experiments. The methyltransferase PseC from the pathway was biochemically characterized to be an iterative methyltransferase that catalyzes off-NRPS line di-methylation on an amine group.