StnK2 catalysing a Pictet–Spengler reaction involved in the biosynthesis of the antitumor reagent streptonigrin. Issue 47 (28th November 2018)

• Record Type: Journal Article
• Authors: Wang, Xiaozheng; Kong, Dekun; Huang, Tingting; Deng, Zixin; Lin, Shuangjun
• Is Part Of: Organic & biomolecular chemistry. Volume 16:Issue 47(2018)
• Page Start: 9124
• Page End: 9128
• Publication Date: 2018-11-28
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c8ob02710b
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : StnK2 is a new Pictet–Spenglerase specifically catalyzing a (1 R, 3 S, 4 S )-tetrahydro-β-carboline scaffold as the biosynthetic intermediate 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 (2 S, 3 S )-β-methyl tryptophan andd -erythrose-4-phosphate. StnK2 can tolerate the alteration of tryptophan but only acceptd -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.