beta-methyltryptophan and tryptoline

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.

Topics: Antibiotics, Antineoplastic; Biosynthetic Pathways; Carbolines; Stereoisomerism; Streptomyces; Streptonigrin; Substrate Specificity; Tryptophan