Carbon supports serve as an essential framework for ensuring electrical connectivity while enabling the uniform dispersion and stabilization of nanocatalysts in electrochemical energy conversion devices. Beyond their roles in mechanical stabilization and electrical conduction, however, recent studies have shown that heteroatom incorporation (e.g., via doping or surface functionalization) on the carbon surface profoundly tailors catalyst-support interfacial properties, which leads to improved physical anchoring or modulated electronic structure of active sites. However, fundamental understanding of the catalytic promotion by such a heteroatom-introduced carbon surface has remained elusive because of a limited systematic approach on model catalysts and in-depth analyses. Herein, we designed Pt-based model catalysts using a nitrogen-functionalized carbon support, prepared via controlled urea annealing. Using comprehensive characterizations of X-ray and nuclear magnetic resonance spectroscopies, we identified the presence of Lewis-acidic nitrogen species stabilized by the extended pi-conjugation network of the carbon matrix. Pt nanoparticles deposited on the nitrogen-functionalized carbon surface reveal a systematic down-shift in d-band energy level, which is associated with distinct electronic coupling between Pt sites and nitrogen group. Oxygen reduction reaction, as a model electrocatalysis, showed enhanced activity with increasing nitrogen modification of the carbon support, consistent with electronic structure modulation of the Pt sites. Moreover, the nitrogen functionalization enhances catalyst durability through increased nanoparticle anchoring and suppressing carbon corrosion. This study underscores the crucial role of interfacial electronic structure between support material and active material as another key descriptor to steer catalytic performance and durability.

Tinospora crispa (Menispermaceae) has been traditionally consumed as a functional food and herbal remedy in Southeast Asia, notably in Thailand and India. cis-Clerodane-type diterpenoids represent the characteristic and predominant metabolites of the genus Tinospora. Chemical investigation of a MeOH extract of T. crispa leaves, guided by LC/MS analysis coupled with an in-house UV spectral library, led to the isolation of five compounds (1–5), including four new cis-clerodane-type diterpenoids (1–4). Their structures were elucidated by 1D and 2D NMR spectroscopy, high-resolution mass spectrometry (HR-ESIMS), interproton distance analysis using NOE peak amplitude normalization for improved cross-relaxation (PANIC), Snatzke’s method, and computational ECD and DP4⁺ probability calculations. The isolated compounds (1–5) were evaluated for their anticancer potential in both liver (Hepa1c1c7, Hepa1-6) and lung (LLC1, A549) cancer cell lines. All compounds 1–5 reduced A549 cell viability by approximately 70

Terpenoids are attractive targets for sustainable biomanufacturing because of their structural diversity and potential applications in fuels and high-value chemicals. Among sesquiterpenes, γ-curcumene is a promising yet underexplored molecule, and its efficient microbial production has not been established. In this study, we identified a previously uncharacterized γ-curcumene synthase PaCS from Parthenium argentatum and evaluated its use for microbial γ-curcumene production in metabolically engineered Escherichia coli. Sequence analysis revealed that PaCS is phylogenetically distinct from the previously reported γ-curcumene synthase from Pogostemon cablin. When expressed in an E. coli strain carrying a heterologous mevalonate pathway, PaCS predominantly produced γ-curcumene, with only minor formation of (−)-α-bisabolol. Product identity was confirmed by GC–MS and NMR analyses. Biochemical characterization of recombinant PaCS showed maximal activity at 35 °C and pH 8.5, with Mg²⁺ as the preferred divalent metal ion. For microbial production, culture conditions and host background were evaluated, and the evolved strain SBA01 showed the best performance. In fed-batch fermentation, the engineered strain produced up to 1.1 g/L γ-curcumene in terrific broth and 1.03 g/L in modified R medium. In addition, purified γ-curcumene was chemically hydrogenated to bisabolane and dihydro-ar-curcumene, demonstrating its utility as a precursor for fuel-related sesquiterpene hydrocarbons. This study establishes a microbial production platform for γ-curcumene using a novel γ-curcumene synthase from P. argentatum and metabolically engineered E. coli. The results expand the available terpene synthase toolbox and provide a foundation for the biosynthesis and downstream upgrading of γ-curcumene-derived molecules. These findings support the broader use of synthetic biology and metabolic engineering for the production of non-native sesquiterpenes from renewable carbon sources.

The compound [N(C2H5)4]2CdBr4, an organic-inorganic hybrid compound, has garnered attention for its potential applications across various fields. In this study, single crystals of [N(C2H5)4]2CdBr4 were grown, and two distinct phase transition temperatures were identified: approximately 232 K (T C1) and 476 K (T C2). Single-crystal X-ray diffraction analysis at 300 K revealed a tetragonal structure belonging to the space group P4̄21 m. The thermal properties of the material were also briefly examined. Interestingly, while the 1H NMR chemical shifts exhibited minimal variation around T C1, the 13C NMR spectra showed a noticeable change in the number of peaks, suggesting a structural phase transition. These observations indicate that the crystal retains a tetragonal structure above T C1 but transitions to a phase with lower symmetry below this temperature. Furthermore, 113Cd NMR chemical shifts showed a significantly more pronounced change near T C1 compared to the shifts observed for 1H and 13C. This behavior reflects alterations in the local electronic environment around the Cd2+ ions, implying reconfiguration of the surrounding atomic framework. Additionally, the spin-lattice relaxation times for 1H and 13C, which are related to molecular motion, were nearly identical for both CH2 and CH3 groups in [N(C2H5)4] cations. The phase transition observed at T C1 is thus attributed to substantial structural rearrangements, particularly involving changes in atomic coordinates and the rotation of the CdBr4 2- tetrahedra.

All-solid-state sodium batteries (ASSSB) are emerging as a viable energy storage technology due to their cost-effectiveness and high energy density. Halide-based electrolytes have shown potential due to their compatibility with high-voltage cathodes. However, most efforts to improve their sluggish ionic transport have focused on inducing amorphization via mechanochemical processes, leaving the direct impact of defect formation relatively unexplored. We demonstrate that introducing Schottky defects, specifically Na and Cl vacancies in NaTaCl6, significantly increases ionic conductivity to 4.77 x 10-4 S/cm without amorphization. Comprehensive experimental analyses and first-principles calculations reveal that these vacancies diversify the local Na environments, thereby lowering energy barriers. Furthermore, while high-energy ball milling effectively promotes partial amorphization, it also triggers unregulated defect formation, resulting in a wide range of conductivities. Our findings highlight the importance of defect engineering as both an alternative and complementary strategy to amorphization, offering a new route for designing high-performance sodium-based solid electrolytes.

The design of organic–peptide hybrids has the potential to combine our vast knowledge of protein design with small molecule engineering to create hybrid structures with complex functions. Here, we describe the computational design of a photoswitchable Ca 2+ -binding organic–peptide hybrid. The designed molecule, designated Ca 2+ -binding switch (CaBS), combines an EF-hand motif from classical Ca 2+ -binding proteins such as calmodulin with a photoswitchable group that can be reversibly isomerized between a spiropyran (SP) and merocyanine (MC) state in response to different wavelengths of light. The MC/SP group acts both as a photoswitch as well as an optical sensor of Ca 2+ binding. Photoconversion of the SP to the corresponding MC unmasks an acidic phenol, which CaBS uses as an integral part of both its Ca 2+ -binding site as well as its tertiary and quaternary structure. By design, the SP state of CaBS is monomeric, while the Ca 2+ -bound form of the MC state is an obligate dimer, with two Ca 2+ -binding sites formed at the interface of a domain-swapped dimer. Thus, light and Ca 2+ were expected to serve as an “AND gate” that powers a change in backbone structure/dynamics, oligomerization state, and fluorescence properties of the designed molecule. CaBS was designed using Rosetta and molecular dynamics simulations, and experimentally characterized by nuclear magnetic resonance, isothermal titration calorimetry, and optical titrations. These data illustrate the potential of combining small molecule engineering with de novo protein design to develop sensors whose conformation, association state, and optical properties respond to multiple environmental cues.

C20- and C22-dihydroxy fatty acids (DiHFAs) are bioactive lipid mediators (LMs) in humans. Among them, leukotrienes are inflammatory mediators, whereas resolvins generated by M2 macrophages in humans are anti-inflammatory mediators. However, the synthesis of LMs by chemical or biological methods is inefficient. Here, we discovered a double-oxygenating arachidonate (ARA) 15R-lipoxygenase (15R-LOX) with the highest catalytic activity among the reported ARA LOXs. Cells expressing double-oxygenating 15R-LOX converted ARA, eicosapentaenoic acid, and docosahexaenoic acid (DHA) and DHA-rich fish oil hydrolyzates into 5R,15R-dihydroxyeicosatetraenoic acid, 5R,15R-dihydroxyeicosapentaenoic acid, and 7R,17R-dihydroxydocosahexaenoic acid as isomers of leukotriene B4, resolvin E4, and resolvin D5, which were identified as new compounds, within 1.5 h, with concentrations >1.5 g L-1, conversions >77% (w/w), and productivity >1.0 g L-1 h(-1), respectively. Double-oxygenating 15R-LOX was altered to single-oxygenating 15R-LOX by the L606F mutation using structure-guided engineering. Cells expressing single-oxygenating 15R-LOX produced 15R-hydroxyeicosatetraenoic acid, 15R-hydroxyeicosapentaenoic acid, and 17R-hydroxydocosahexaenoic acid, respectively. These results demonstrated that the six medicinally important LMs could be prepared from C20- and C22-polyunsaturated fatty acids and inexpensive DHA-rich fish oil hydrolyzates by cost-effective, eco-friendly, and efficient biosynthesis using the discovered double-oxygenating and engineered single-oxygenating LOXs.

This work shows that hollow Ru/RuO2 nanoparticles having nanoparticulate shells (HN-Ru/RuO2) can be prepared using hollow microporous organic polymers with Ru species (H-MOP-Ru) as precursors. Using silica spheres as templates, H-MOPs were prepared through the Sonogashira-Hagihara coupling of 1,3,5-triethynylbenzene with 2,3-ethoxymethylenedioxy-1,4-diiodobenzene. Acid hydrolysis of cyclic ethyl orthoformate protecting groups generated catechol moieties to form H-MOP-Cat. Then, H-MOP-Ru was obtained by incorporating Ru species into H-MOP-Cat. Heat-treatment of H-MOP-Ru under air induced the formation of HN-Ru/RuO2 with a diameter of 61 nm and shells consisting of 6-7 nm nanoparticles. Due to the hollow structure and nanoparticulate shells, HN-Ru/RuO2 showed a high surface area of 80 m(2) g(-1) and a pore volume of 0.18 cm(3) g(-1). The HN-Ru/RuO2 showed enhanced electrocatalytic performance for the oxygen evolution reaction (OER) with an overpotential of 295 mV @ 10 mA cm(-2) and a Tafel slope of 46 mV dec(-1) in alkaline electrolyte, compared with control RuO2 such as commercial Ru/RuO2 nanoparticles (A-Ru/RuO2) and home-made Ru/RuO2 nanoparticles (N-Ru/RuO2) prepared via the same synthetic procedure as HN-Ru/RuO2. While HN-Ru/RuO2 inevitably contained Pd originated from coupling catalysts, it showed superior performance to Ru/RuO2 nanoparticles with the same Pd content (N1-Ru/RuO2), indicating that the efficient electrocatalytic performance of HN-Ru/RuO2 is attributable to its hollow structure and nanoparticulate shells.

A hollow catalyst bearing N-heterocyclic carbene (NHC)-Fe species was synthesized using a hollow microporous organic polymer (HMOP) as a template. In the presence of HMOP, the Friedel-Crafts reaction of 1,3,5-tri(bromomethyl)benzene induced the loading of hypercrosslinked polymer (HCP) onto HMOP. The resultant HMOP@HCP material bearing benzyl bromide groups could be further modified with N-methylimidazole to form HMOP@HCP bearing imidazolium salt (HMOP@HCP-Im). The use of KO t Bu, followed by Fe coordination, generated HMOP@HCP bearing NHC-Fe species (HMOP@HCP-Fe). HMOP@HCP-Fe showed superior catalytic performance to nonhollow HCP-Fe in the transesterification of dimethyl furan 2,5-dicarboxylate to furan diols, polymer platforms of polyurethane. In addition, HMOP@HCP-Fe showed near-quantitative yields for five successive catalytic runs.

Codonopsis lanceolata, commonly known as the bonnet bellflower or deodeok, is primarily found in Eastern Asia. Its roots have been used traditionally across Asia to treat various ailments such as bronchitis, coughs, asthma, and inflammation. In our ongoing efforts to discover bioactive natural products, a phytochemical investigation of the n-BuOH fraction of C. lanceolata root extracts led to the isolation and identification of a new indole alkaloid N-glycoside, deodeokaloid (D-indole-3-lactic acid N-β-D-glucopyranoside) (1), alongside known compounds tangshenoside I (2), tangshenoside IV (3), and chlorogenic acid (4) through HPLC purification. The structure of the new compound 1 was elucidated using 1D and 2D NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). Its absolute configuration was determined through a combination of DP4+ probability analysis and chemical reactions. The isolated compounds 1–4 were evaluated for their anti-Helicobacter pylori and antioxidant activities. In the anti-H. pylori assay, compound 3 showed antibacterial activity similar to that of quercetin as the positive control, inhibiting the bacterial growth by 36.8%. Compound 4 exhibited the most potent antioxidant activity, with an ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate)] radical scavenging activity of 1624.7 mmol TE/mol and a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging capacity of 707.5 mmol Trolox equivalent (TE)/mol. Compounds 2–4 displayed significant intracellular reactive oxygen species (ROS) scavenging capacity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. This study highlights C. lanceolata roots as a promising natural source of bioactive compounds with potential therapeutic applications.

Salix koreensis Anderss (Salicaceae), commonly referred to as Korean willow, is native to East Asia, particularly Korea and China, and it has been used in traditional Korean folk medicine for its potent anti-inflammatory, analgesic, and antioxidant properties. In our ongoing research efforts to discover biologically new natural products, phytochemical analysis on an ethanolic extract of S. koreensis twigs yielded the isolation and identification of ten phenolic compounds (1–10), including a newly discovered phenolic glycoside (1) named isograndidentatin D, isolated via HPLC purification. The structure of compound 1 was determined through extensive 1D and 2D NMR spectral data analysis and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). Its absolute configuration was established using DP4+ probability analysis combined with gauge-including atomic orbital NMR chemical shift calculations and chemical reaction methods. The other known compounds were identified as isograndidentatin B (2), trichocarposide (3), glanduloidin C (4), tremuloidin (5), 3-O-acetylsalicin (6), 2-O-acetylsalicin (7), salicin (8), salireposide (9), and coumaric acid (10), confirmed by comparing their NMR spectra with previously reported data and further verified through liquid chromatography/mass spectrometry (LC/MS) analysis. The isolated compounds 1–10 were tested for their anti-Helicobacter pylori activities. Among these, compounds 4 and 5 demonstrated moderate anti-H. pylori activity at a concentration of 100 μM. Specifically, compound 5 showed an inhibitory activity of 35.9 ± 5.4%, making it slightly more potent than compound 4, with 34.0 ± 1.0% inhibition. These results were comparable to that of quercetin, a known anti-H. pylori agent used as a positive control in this study, which showed 38.4 ± 2.3% inhibition. The remaining compounds exhibited very weak inhibitory effects. This study highlights the potential of S. koreensis twigs as a valuable natural source of bioactive compounds for therapeutic applications against H. pylori.

Protectins, 10,17-dihydroxydocosahexaenoic acids (10,17-DiHDHAs), are belonged to specialized pro-resolving mediators (SPMs). Protectins are generated by polymorphonuclear leukocytes in humans and resolve inflammation and infection in trace amounts. However, the quantitative production of protectin Dx 10-epimer (10-epi PDX, 10R,17S-4Z,7Z,11E,13Z,15E,19Z-DiHDHA) has been not attempted to date. In this study, 10-epi PDX was quantitatively produced from docosahexaenoic acid (DHA) by serial whole-cell biotransformation of Escherichia coli expressing arachidonate (ARA) 8R-lipoxygenase (8R-LOX) from the coral Plexaura homomalla and E. coli expressing ARA 15S-LOX from the bacterium Archangium violaceum. The optimal bioconversion conditions to produce 10R-hydroxydocosahexaenoic acid (10R-HDHA) and 10-epi PDX were pH 8.0, 30°C, 2.0 mM DHA, and 4.0 g/L cells; and pH 8.5, 20°C, 1.4 mM 10R-HDHA, and 1.0 g/L cells, respectively. Under these optimized conditions, 2.0 mM (657 mg/L) DHA was converted into 1.2 mM (433 mg/L) 10-epi PDX via 1.4 mM (482 mg/L) 10R-HDHA by the serial whole-cell biotransformation within 90 min, with a molar conversion of 60% and volumetric productivity of 0.8 mM/h (288 mg/L/h). To the best of our knowledge, this is the first quantitative production of 10-epi PDX. Our results contribute to the efficient biocatalytic synthesis of SPMs.

A targeted metabologenomic method was developed to selectively discover terminal oxazole-bearing natural products from bacteria. For this, genes encoding oxazole cyclase, a key enzyme in terminal oxazole biosynthesis, were chosen as the genomic signature to screen bacterial strains that may produce oxazole-bearing compounds. Sixteen strains were identified from the screening of a bacterial DNA library (1,000 strains) using oxazole cyclase gene-targeting polymerase chain reaction (PCR) primers. The PCR amplicon sequences were subjected to phylogenetic analysis and classified into nine clades. 1 H− 13 C coupled-HSQC NMR spectra obtained from the culture extracts of the hit strains enabled the unequivocal detection of the target compounds, including five new oxazole compounds, based on the unique 1 J CH values and chemical shifts of oxazole: lenzioxazole ( 1 ) possessing an unprecedented cyclopentane, permafroxazole ( 2 ) bearing a tetraene conjugated with carboxylic acid, tenebriazine ( 3 ) incorporating two modified amino acids, and methyl-oxazolomycins A and B ( 4 and 5 ). Tenebriazine displayed inhibitory activity against pathogenic fungi, whereas methyl-oxazolomycins A and B ( 4 and 5 ) selectively showed anti-proliferative activity against estrogen receptor-positive breast cancer cells. This metabologenomic method enables the logical and efficient discovery of new microbial natural products with a target structural motif without the need for isotopic labeling.

Withdrawal Statement The authors have withdrawn their manuscript owing to correct and validate the errors before resubmitting. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

This work suggests an engineering methodology for catalytic 2D materials to achieve more efficient catalytic systems. Zinc gallate (ZnG), a Lewis acidic material with a thin 2D morphology, can easily form aggregates through layer-layer packing. Inner parts of ZnG aggregates would have difficulty in interacting with substrates. By coating hollow microporous organic polymer (H-MOP) supports with ZnG, the catalytic performance of ZnG can be enhanced due to facilitated contact of substrates with Zn species in shells. H-MOP@ZnG-2 with an optimal ZnG coating showed a much enhanced catalytic performance for the reductive carbon dioxide fixation with amines to formamides compared with ZnG. Various amines can be utilized in the reductive carbon dioxide fixation to formamides. In addition, H-MOP@ZnG-2 showed recyclability, maintaining its catalytic performance for five successive reactions.

Salix chaenomeloides Kimura, commonly known as pussy willow, is a deciduous shrub and tree belonging to the Salicaceae family. The genus Salix spp. has been known as a healing herb for the treatment of fever, inflammation, and pain relief. The current study aimed to investigate the potential bioactive natural products from S. chaenomeloides leaves and evaluate their antibacterial activity against Helicobacter pylori. A phytochemical investigation of the ethanol (EtOH) extract of S. chaenomeloides leaves led to the isolation of 13 phenolic compounds (1–13) from the ethyl acetate (EtOAc) fraction, which showed antibacterial activity against H. pylori strain 51. The chemical structure of a new phenolic glycoside, chaenomelin (1), was established by a detailed analysis of 1D and 2D (1H-1H correlation spectroscopy (COSY), heteronuclear single-quantum coherence (HSQC), and heteronuclear multiple-bond correlation (HMBC)) nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), and chemical reactions. The other known compounds were identified as 5-O-trans-p-coumaroyl quinic acid methyl ester (2), tremulacin (3), citrusin C (4), benzyl 3-O-β-d-glucopyranosyl-7-hydroxybenzoate (5), tremuloidin (6), 1-[O-β-d-glucopyranosyl(1→2)-β-d-glucopyranosyl]oxy-2-phenol (7), arbutin cinnamate (8), tremulacinol (9), catechol (10), 4-hydroxybenzaldehyde (11), kaempferol 3-rutinoside (12), and narcissin (13), based on the comparison of their NMR spectra with the reported data and liquid chromatography/mass spectrometry (LC/MS) analysis. The isolated compounds were evaluated for antibacterial activity against H. pylori strain 51. Among the isolates, 1-[O-β-d-glucopyranosyl(1→2)-β-d-glucopyranosyl]oxy-2-phenol (7) and arbutin cinnamate (8) exhibited antibacterial activity against H. pylori strain 51, with inhibitions of 31.4% and 33.9%, respectively, at a final concentration of 100 μM. These results were comparable to that of quercetin (38.4% inhibition), which served as a positive control. Generally, these findings highlight the potential of the active compounds 7 and 8 as antibacterial agents against H. pylori.

The logical and effective discovery of macrolactams, structurally unique natural molecules with diverse biological activities, has been limited by a lack of targeted search methods. Herein, a targeted discovery method for natural macrolactams was devised by coupling genomic signature-based PCR screening of a bacterial DNA library with spectroscopic signature-based early identification of macrolactams. DNA library screening facilitated the efficient selection of 43 potential macrolactam-producing strains (3.6% of 1,188 strains screened). The PCR amplicons of the amine-deprotecting enzyme-coding genes were analyzed to predict the macrolactam type (α-methyl, α-alkyl, or β-methyl) produced by the hit strains. 1H-15N HSQC-TOCSY NMR analysis of 15N-labeled culture extracts enabled macrolactam detection and structural type assignment without any purification steps. This method identified a high-titer Micromonospora strain producing salinilactam (1), a previously reported α-methyl macrolactam, and two Streptomyces strains producing new α-alkyl and β-methyl macrolactams. Subsequent purification and spectroscopic analysis led to the structural revision of 1 and the discovery of muanlactam (2), an α-alkyl macrolactam with diene amide and tetraene chromophores, and concolactam (3), a β-methyl macrolactam with a [16,6,6]-tricyclic skeleton. Detailed genomic analysis of the strains producing 1-3 identified putative biosynthetic gene clusters and pathways. Compound 2 displayed significant cytotoxicity against various cancer cell lines (IC50 = 1.58 μM against HCT116), whereas 3 showed inhibitory activity against Staphylococcus aureus sortase A. This genomic and spectroscopic signature-based method provides an efficient search strategy for new natural macrolactams and will be generally applicable for the discovery of nitrogen-bearing natural products.

Chemical structures of five coals from Mongolia were studied using solid-state C-13 NMR and oil and gas potential as well as yields of liquefaction products of the coals have been predicted. Pennsylvanian ZG, Upper Permian TT and Lower-Middle Jurassic AT-5 coals might have more potential for gas due to abundant aliphatic and aromatic CH3 carbons. Lower-Middle Jurassic KH coal probably has more potential for oil because of its increased CH2 content. Lower Cretaceous SO-3 coal may have more potential for gas, but significant amount of non-hydrocarbon gases could also be generated simultaneously. The prediction of yields of liquefaction product shows that ZG, TT and AT-5 and KH coals could yield similar hydrocarbon gas, oil and residue. Cretaceous SO-3 coal is predicted to give the lowest yields of oil, hydrocarbon gas and residue compared with others. KH sample has the highest oil yield due to its high content of CH2. Keywords: coal, petroleum potential, NMR, Mongolia

A targeted and logical discovery method was devised for natural products containing piperazic acid (Piz), which is biosynthesized from ornithine by l-ornithine N-hydroxylase (KtzI) and N-N bond formation enzyme (KtzT). Genomic signature-based screening of a bacterial DNA library (2020 strains) using polymerase chain reaction (PCR) primers targeting ktzT identified 62 strains (3.1%). The PCR amplicons of KtzT-encoding genes were phylogenetically analyzed to classify the 23 clades into two monophyletic groups, I and II. Cultivating hit strains in media supplemented with 15NH4Cl and applying 1H-15N heteronuclear multiple bond correlation (HMBC) along with 1H-15N heteronuclear single quantum coherence (HSQC) and 1H-15N HSQC-total correlation spectroscopy (HSQC-TOCSY) NMR experiments detected the spectroscopic signatures of Piz and modified Piz. Chemical investigation of the hit strains prioritized by genomic and spectroscopic signatures led to the identification of a new azinothricin congener, polyoxyperuin B seco acid (1), previously reported chloptosin (2) in group I, depsidomycin D (3) incorporating two dehydropiperazic acids (Dpz), and lenziamides A and B (4 and 5), structurally novel 31-membered cyclic decapeptides in group II. By consolidating the phylogenetic and chemical analyses, clade-structure relationships were elucidated for 19 of the 23 clades. Lenziamide A (4) inhibited STAT3 activation and induced G2/M cell cycle arrest, apoptotic cell death, and tumor growth suppression in human colorectal cancer cells. Moreover, lenziamide A (4) resensitized 5-fluorouracil (5-FU) activity in both in vitro cell cultures and the in vivo 5-FU-resistant tumor xenograft mouse model. This work demonstrates that the genomic and spectroscopic signature-based searches provide an efficient and general strategy for new bioactive natural products containing specific structural motifs.