Journal
ANTIBIOTICS-BASEL
Volume 11, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/antibiotics11101444
Keywords
1-benzazepine; l-kynurenine; genome mining; biosynthesis; iterative methyltransferase
Categories
Funding
- National Key Research and Development Program of China [2018YFA0901900]
- National Natural Science Foundation of China [31971345]
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In this study, a biosynthetic gene cluster from Neosartorya pseudofischeri was discovered, and the biosynthetic pathway of pseudofisnins was elucidated. The methyltransferase PseC in the pathway was also characterized.
l-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 l-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 Neosartorya pseudofischeri 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.
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