Issue 47, 2018

StnK2 catalysing a Pictet–Spengler reaction involved in the biosynthesis of the antitumor reagent streptonigrin

Abstract

Streptonigrin (STN, 1) is a highly functionalized aminoquinone alkaloid antibiotic with broad and potent antitumor activity. Previous isotope-labelling and genetic studies suggested that a β-carboline alkaloid should be a key intermediate of STN biosynthesis and formed via a Pictet–Spengler (PS) reaction. Herein, StnK2 was biochemically characterized to be a Pictet–Spenglerase (PSase) catalysing the formation of a tetrahydro-β-carboline (TH-βC) scaffold from (2S,3S)-β-methyl tryptophan and D-erythrose-4-phosphate. StnK2 can tolerate the alteration of tryptophan but only accept D-erythrose-4-phosphate as the aldehyde substrate, and StnK2 was identified to be R-specific for the newly formed chiral center. This work increases the diversities of Pictet–Spenglerase in nature and set a stage for the generation of streptonigrin derivatives by precursor-directed pathway engineering based on the flexible substrate selectivity of StnK2.

Graphical abstract: StnK2 catalysing a Pictet–Spengler reaction involved in the biosynthesis of the antitumor reagent streptonigrin

Supplementary files

Article information

Article type
Communication
Submitted
31 oct. 2018
Accepted
19 nov. 2018
First published
28 nov. 2018

Org. Biomol. Chem., 2018,16, 9124-9128

StnK2 catalysing a Pictet–Spengler reaction involved in the biosynthesis of the antitumor reagent streptonigrin

X. Wang, D. Kong, T. Huang, Z. Deng and S. Lin, Org. Biomol. Chem., 2018, 16, 9124 DOI: 10.1039/C8OB02710B

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