Coculture of Marine Streptomyces sp. With Bacillus sp. Produces a New Piperazic Acid-Bearing Cyclic Peptide

Microbial culture conditions in the laboratory, which conventionally involve the cultivation of one strain in one culture vessel, are vastly different from natural microbial environments. Even though perfectly mimicking natural microbial interactions is virtually impossible, the cocultivation of multiple microbial strains is a reasonable strategy to induce the production of secondary metabolites, which enables the discovery of new bioactive natural products. Our coculture of marine Streptomyces and Bacillus strains isolated together from an intertidal mudflat led to discover a new metabolite, dentigerumycin E (1). Dentigerumycin E was determined to be a new cyclic hexapeptide incorporating three piperazic acids, N-OH-Thr, N-OH-Gly, β-OH-Leu, and a pyran-bearing polyketide acyl chain mainly by analysis of its NMR and MS spectroscopic data. The putative PKS-NRPS biosynthetic gene cluster for dentigerumycin E was found in the Streptomyces strain, providing clear evidence that this cyclic peptide is produced by the Streptomyces strain. The absolute configuration of dentigerumycin E was established based on the advanced Marfey's method, ROESY NMR correlations, and analysis of the amino acid sequence of the ketoreductase domain in the biosynthetic gene cluster. In biological evaluation of dentigerumycin E (1) and its chemical derivatives [2-N,16-N-deoxydenteigerumycin E (2) and dentigerumycin methyl ester (3)], only dentigerumycin E exhibited antiproliferative and antimetastatic activities against human cancer cells, indicating that N-OH and carboxylic acid functional groups are essential for the biological activity

High Bandwidth and Highly Available Packet Buffer Design Using Multi-Retention Time MRAM

Significant challenges are posed in the design of routers and switches by the explosive growth of internet traffic and the stringent requirements for high availability in the research area of computer networks. Ensuring both high performance and system availability is crucial. To achieve this, recent advancements have turned to the utilization of non-volatile memories, such as magnetic RAM (MRAM) and phase-change memory (PCM), in routing lookup tables and packet buffers of routers and switches. However, the use of non-volatile memories show limitations in scaling with respect to bandwidth and capacity. With the increasing clock speed of the IO bus, high-capacity memories like PCM exhibit limited scalability in performance since accessing the cells in the array does not show significant improvement. Meanwhile, attempts to enhance the capacity of low-access-latency non-volatile memories like spin-transfer torque MRAM (STT-MRAM) through smaller cell sizes result in an adverse impact on the write time. The goal of this study is to design a packet buffer that can provide high bandwidth and ensure high availability. To achieve this, a multi-retention time MRAM-based packet buffer is presented, along with a packet mapping method, which aims to overcome the scalability challenge while ensuring high availability. The two-tier packet buffer (TT-PB) structure implements a small/fast MRAM combined with a large/slow MRAM, which outperforms the baseline MRAM/PCM hybrid memory-based packet buffer by up to 16% and 58% for 1.6 and 3.2 GHz IO bus clocks. For input, internet-mix packet traffic is utilized to depict realistic internet traffic. Moreover, the proposed latency-aware multi-retention time MRAM-based packet buffer structure (MR-PB) consists of short and long retention time MRAM partitions. It identifies the buffering latency demands of various packets and writes the packets into partitions that have sufficient retention time to accommodate the required buffering latencies, thereby achieving an optimal write latency for each packet. With this scheme, an additional speedup of up to 5.27% is achieved over TT-PB

QM-HiFSA-Aided Structure Determination of Succinilenes A–D, New Triene Polyols from a Marine-Derived Streptomyces sp.

Based on profiles of secondary metabolites produced by marine bacteria obtained using LC/MS, succinilenes A–D (1–4), new triene polyols, were discovered from a culture of a Streptomyces strain SAK1, which was collected in the southern area of Jeju Island, Republic of Korea. The gross structures of 1–4 were primarily determined through analysis of NMR spectra. The double bond geometries of the succinilenes, which could not be established from conventional 1H NMR spectra because of the highly overlapped olefinic signals, were successfully deciphered using the recently developed quantum-mechanics-driven 1H iterative full spin analysis (QM-HiFSA). Succinilenes A–C (1–3) displayed inhibitory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production, indicating their anti-inflammatory significance. These three compounds (1–3) commonly bear a succinic acid moiety, although succinilene D (4), which did not inhibit NO production, does not have this moiety in its structure. The absolute configurations of succinilenes A–D (1–4) were established through J-based configuration analysis, the modified Mosher’s method following methanolysis, and CD spectral analysis

Separacenes A–D, Novel Polyene Polyols from the Marine Actinomycete, Streptomyces sp.

Separacenes A–D (1–4), novel polyene polyols, were isolated from Streptomyces sp. collected from the southern area of Jeju Island, Korea. The chemical structures of 1–4 were established by NMR, mass, UV, and IR spectroscopy as well as the modified Mosher’s method. Separacenes A–B (1–2), which share an identical planar structure but possess different relative configurations, bear tetraene units flanked by two diol moieties, whereas the stereoisomeric separacenes C–D (3–4) possess a triene moiety between two diol substructures. Separacenes A–D each contain a terminal olefinic methylene. Separacene A displayed inhibitory activity against Candida albicans isocitrate lyase and weak cytotoxicity against both the colon carcinoma cell line HCT-116 and the lung cancer cell line A549

Depsidomycins B and C: New Cyclic Peptides from a Ginseng Farm Soil-Derived Actinomycete

LC/MS-based chemical profiling of a ginseng farm soil-derived actinomycete strain, Streptomyces sp. BYK1371, enabled the discovery of two new cyclic heptapeptides, depsidomycins B and C (1 and 2), each containing two piperazic acid units and a formyl group at their N-terminus. The structures of 1 and 2 were elucidated by a combination of spectroscopic and chemical analyses. These new compounds were determined to possess d-leucine, d-threonine, d-valine, and S-piperazic acid based on the advanced Marfey’s method and a GITC (2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate) derivatization of their hydrolysates, followed by LC/MS analysis. Depsidomycins B and C displayed significant antimetastatic activities against metastatic breast cancer cells (MDA-MB-231)

A New Benzofuran Glycoside and Indole Alkaloids from a Sponge-Associated Rare Actinomycete, Amycolatopsis sp.

Three new secondary metabolites, amycofuran (1), amycocyclopiazonic acid (2), and amycolactam (3), were isolated from the sponge-associated rare actinomycete Amycolatopsis sp. Based on combined spectroscopic analyses, the structures of 1–3 were determined to be a new benzofuran glycoside and new indole alkaloids related to cyclopiazonic acids, a class that has previously only been reported in fungi. The absolute configurations of 1 and 3 were deduced by ECD calculations, whereas that of 2 was determined using the modified Mosher method. Amycolactam (3) displayed significant cytotoxicity against the gastric cancer cell line SNU638 and the colon cancer cell line HCT116

Mohangic Acids A–E, <i>p</i>‑Aminoacetophenonic Acids from a Marine-Mudflat-Derived <i>Streptomyces</i> sp.

Mohangic acids A–E (<b>1</b>–<b>5</b>) were isolated from a marine <i>Streptomyces</i> sp. collected from a mudflat in Buan, Republic of Korea. Comprehensive spectroscopic analysis revealed that the mohangic acids are new members of the <i>p</i>-aminoacetophenonic acid class. The relative and absolute configurations of the mohangic acids were determined by <i>J</i>-based configuration analysis and by the application of bidentate chiral NMR solvents followed by ¹³C NMR analysis, chemical derivatization, and circular dichroism spectroscopy. Mohangic acid E (<b>5</b>), which is the first glycosylated compound in the <i>p</i>-aminoacetophenonic acid family, displayed significant quinone reductase induction activity