|
type |
Journal Article |
authors |
Lin Z, Ji J, Zhou S, Zhang F, Wu J, Guo Y, Liu W |
title |
Processing 2-Methyl-l-Tryptophan through Tandem Transamination and Selective Oxygenation Initiates Indole Ring Expansion in the Biosynthesis of Thiostrepton |
journal |
J Am Chem Soc |
Activity |
tsra |
Family |
tsra |
sel |
selected |
ui |
28820583 |
year |
(2017) |
volume |
39 |
number |
35 |
pages |
12105-12108 |
| |
keywords |
doi: 10.1021/jacs.7b05337 |
abstract |
Thiostrepton (TSR), an archetypal member of the family of ribosomally synthesized and post-translationally modified thiopeptide antibiotics, possesses a biologically important quinaldic acid (QA) moiety within the side-ring system of its characteristic thiopeptide framework. QA is derived from an independent l-Trp residue; however, its associated transformation process remains poorly understood. We here report that during the formation of QA, the key expansion of an indole to a quinoline relies on the activities of the pyridoxal-5'-phosphate-dependent protein TsrA and the flavoprotein TsrE. These proteins act in tandem to process the precursor 2-methyl- l-Trp through reversible transamination and selective oxygenation, thereby initiating a highly reactive rearrangement in which selective C2-N1 bond cleavage via hydrolysis for indole ring-opening is closely coupled with C2'-N1 bond formation via condensation for recyclization and ring expansion in the production of a quinoline ketone intermediate. This indole ring-expansion mechanism is unusual, and represents a new strategy found in nature for l-Trp-based functionalization. |
last changed |
2018/04/03 14:52 |
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