Naseseazines A and B: A New Dimeric Diketopiperazine Framework from a Marine-Derived Actinomycete, Streptomyces sp.

Abstract

Chemical analysis of a Streptomyces sp. (CMB-MQ030) isolated from a Fijian marine sediment yielded two new diketopiperazines, naseseazines A and B (1, 2), featuring a new dimeric framework. Structures were determined by detailed spectroscopic analysis and C(3) Marfey's analysis.

Evaluation of Biosynthetic Pathway and Engineered Biosynthesis of Alkaloids

“…These two compounds were analogs of the homodimeric product 5 previously produced ( Figure 4). Elucidation of the chemical structures 7 and 8 showed 7 to be a new compound and 8 to be naseseazine B isolated recently from a marine-dwelling streptomycete bacterium [15]. Dimerization in 7 and 8 did not form the C3-C3' linkage found in 1, 5 and 6.…”

“…. Proposed mechanism of DtpC-catalyzed formation of dimerization products (−)-dibrevianamide F 5 [9], a new compound 7 [14] and naseseazine B 8 [15]. Radical-mediated formation of 7 and 8 is thought to be initiated by DtpC forming a radical at N1 instead of N10 as proposed for the formation of 5.…”

“…To put this bioproduction approach into practice, detailed understanding of the biosynthetic mechanism of this class of natural products is essential. Therefore, there has been a considerable study on the subject involving gene isolation [28][29][30], substrate feeding experiments Proposed mechanism of DtpC-catalyzed formation of dimerization products (−)-dibrevianamide F 5 [9], a new compound 7 [14] and naseseazine B 8 [15]. Radical-mediated formation of 7 and 8 is thought to be initiated by DtpC forming a radical at N1 instead of N10 as proposed for the formation of 5.…”

“…Based on those experiments, the ergot biosynthetic pathway was determined to be initiated by the prenylation of L-tryptophan with DMAPP that forms 4-(γ,γ-dimethylallyl) tryptophan (15) (Figure 10) [57,58]. The next step involves the N-methylation of 15 to yield 4-dimethyl-L-abrine (16) [59].…”

Glionitrin B, a Cancer Invasion Inhibitory Diketopiperazine Produced by Microbial Coculture

“…10À14 The structural diversity of these diketopiperazines is achieved through subsequent reactions, such as cyclization, 15 prenylation, 16 and dimerization. 17,18 2,5-Diketopiperazine derivatives have a wide range of biological activities, including as modulators of plasminogen activator inhibitor (PAI)-1, 19 platelet activating factor antagonists, 20 cell cycle inhibitors, 21 tryptase inhibitors, 22 antifouling activities, 23 and oxytocin antagonists. 24 In the present study, the diketopiperazine disulfides glionitrin A (2) and gliotoxin (4) exhibited significant cytotoxicity against a DU145 human prostate cancer cell line, whereas glionitrin B (1) and 3 did not effect DU145 cell viability ( Figure S18).…”