Discovery and Biosynthesis of Pepticinnamins G-M Featuring Three Enzymes-Catalyzed Nonproteinogenic Amino Acid Formation.
J Org Chem
; 85(13): 8673-8682, 2020 07 02.
Article
em En
| MEDLINE
| ID: mdl-32489098
ABSTRACT
Since pepticinnamin E was discovered almost 30 years ago, no other pepticinnamin family of natural products has been reported to date. Here, we report the discovery of pepticinnamins G-I (1-3) from a marine Streptomyces sp. PKU-MA01144 and pepticinnamins J-M (4-7) from several mutants, and these new compounds contain different N-methyl-l-alanine and l-tyrosine residues compared to pepticinnamin E. Genome sequencing, heterologous expression, gene deletion, and reconstitution of enzymatic reaction in vitro identified the biosynthetic gene cluster of 1-7 and first experimentally established the biosynthesis of the nonproteinogenic 2-chloro-3-hydroxy-4-methoxy-l-phenylalanine residue by a biopterin-dependent hydroxylase Pep10, an O-methyltransferase Pep9, and a flavin-dependent halogenase Pep1. The biosynthetic research and heterologous expression system in this study set the stage for pathway engineering for more pepticinnamins generation in the future.
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Base de dados:
MEDLINE
Assunto principal:
Streptomyces
/
Produtos Biológicos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article