De Novo Artificial Biosynthesis of 3-Hydroxyphloretin in .

3-Hydroxyphloretin (3-OH phloretin), a dihydrochalcone compound containing a catechol moiety, is naturally present in apples and exhibits potent anti-adipogenic, anti-obesity, and anticancer activities. In this study, we developed a modular co-culture platform enabling the de novo biosynthesis of 3-OH phloretin from glucose in . We demonstrated that 4-coumarate 3-hydroxylase (Sam5), derived from , efficiently catalyzes the hydroxylation of phloretin to 3-OH phloretin.

Protective effect of hygrolansamycin C against corticosterone-induced toxicity and oxidative stress-mediated via autophagy and the MAPK signaling pathway.

Background: Excessive stress, a major problem in modern societies, affects people of all ages worldwide. Corticosterone is one of the most abundant hormones secreted during stressful conditions and is associated with various dysfunctions in the body. In particular, we aimed to investigate the protective effects of hygrolansamycin C (HYGC) against corticosterone-induced cellular stress, a manifestation of excessive stress prevalent in contemporary societies.

A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis.

The pluramycin family of natural products has diverse substituents at the C2 position, which are closely related to their biological activity. Therefore, it is important to understand the biosynthesis of C2 substituents. In this study, we describe the biosynthesis of C2 moieties in sp.

Targeted Isolation of -Acetylcysteine-Containing Angucycline Derivatives from sp. MC16 and Their Antiproliferative Effects.

Liquid chromatography-mass spectrometry (LC-MS/MS)-based molecular networking analysis was applied to sp. MC16. The automatic classification of the MolNetEnhancer module revealed that its major constituent was an angucycline derivative.

Induction of Fungal Secondary Metabolites by Co-Culture with Actinomycete Producing HDAC Inhibitor Trichostatins.

A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without sp.

Rubiflavin G, photorubiflavin G, and photorubiflavin E: Novel pluramycin derivatives from Streptomyces sp. W2061 and their anticancer activity against breast cancer cells.

The pluramycin family of antibiotics comprises angucycline compounds derived from actinomycetes that possess anticancer and antibacterial properties. Pluramycins are structurally characterized by two aminoglycosides linked by a carbon-carbon bond next to the γ-pyrone angucycline backbone. Kidamycins (3, 4) and rubiflavins (6-9) were screened through liquid chromatography-mass spectrometry analysis of the crude extracts of Streptomyces sp.

Hygrolansamycins A-D, -Heterocyclic Macrolides from sp. KCB17JA11.

Six ansamycin derivatives were isolated from the culture broth of sp. KCB17JA11, including four new hygrolansamycins A-D (1-4) and known congeners divergolide O (5) and hygrocin C (6). Compounds 1-5 featured an unusual six-membered -heterocyclic moiety.

Ulleungdolin, a Polyketide-Peptide Hybrid Bearing a 2,4-Di--methyl-β-d-antiarose from sp. 13F051 Co-cultured with 15S071.

A new secondary metabolite, ulleungdolin (), was isolated from the co-culture of an actinomycete, sp. 13F051, and a fungus, 15S071. Based on the NMR, UV, and MS data, it was deduced that the planar structure of comprised an isoindolinone (IsoID) with an octanoic acid, a tripeptide, and a sugar.

Elucidation of the di-c-glycosylation steps during biosynthesis of the antitumor antibiotic, kidamycin.

Kidamycins belong to the pluramycin family of antitumor antibiotics that contain di-C-glycosylated angucycline. Owing to its interesting biological activity, several synthetic derivatives of kidamycins are currently being developed. However, the synthesis of these complex structural compounds with unusual C-glycosylated residues is difficult.

Jejucarbazoles A-C, carbazole glycosides with indoleamine 2,3-dioxygenase 1 inhibitory activity from sp. KCB15JA151.

A bioassay-guided investigation led to the isolation of three new carbazole glycosides, jejucarbazoles A-C (1-3), from sp. KCB15JA151. Their planar structures were elucidated by detailed NMR and MS spectroscopic analysis with a literature study.

Construction of an Artificial Biosynthetic Pathway for Zingerone Production in Using Benzalacetone Synthase from .

Zingerone (vanillylacetone; 4-hydroxy-3-methoxyphenylethyl methyl ketone) is a key component responsible for the pungency of ginger (). In this study, it was confirmed that a type III polyketide synthase (PKS) gene () from exhibits feruloyl-CoA-preferred benzalacetone synthase (BAS) activity. Based on these results, we constructed an artificial biosynthetic pathway for zingerone production from supplemented ferulic acid with 4-coumarate CoA ligase (4CL), PmPKS, and benzalacetone reductase (BAR).

Construction of an Artificial Biosynthetic Pathway for the Styrylpyrone Compound 11-Methoxy-Bisnoryangonin Produced in Engineered .

A cDNA clone (named ), which shows high homology to the known chalcone synthase (CHS)-like type III PKS, was obtained from the leaves of . The PnPKS protein with ferulic acid catalyzed lactonization instead of chalcone or stilbene formation. The new product was characterized as a styrylpyrone, 11-methoxy-bisnoryangonin, which is the lactonization compound of a linear triketide formed as the reaction product of PnPKS protein with ferulic acid.

Ulleunganilines A-C, Trichostatin Analogues Bearing a Modified Side Chain from sp. 13F051.

Three new trichostatin analogues, ulleunganilines A-C (-), and seven known trichostatins (-) were isolated from cultures of sp. 13F051. NMR, UV, and MS data indicated that the planar structures of - consisted of modified side chains in the trichostatic acid moiety.

Angucyclines containing β-ᴅ-glucuronic acid from Streptomyces sp. KCB15JA151.

Two angucyclines, pseudonocardones D (1) and E (2), were isolated from Streptomyces sp. KCB15JA151. The planar structure was elucidated by comprehensive spectroscopic analysis.

A pipecolic acid-rich branched cyclic depsipeptide ulleungamide C from a Streptomyces species induces G0/G1 cell cycle arrest in promyelocytic leukemia cells.

In this study, screening by LC-MS and cytotoxicity-guided isolation led to the identification of ulleungamide C (1), a previously unknown pipecolic acid-rich branched cyclic depsipeptide, from a soil actinobacterium Streptomyces sp. KCB13F003. The structure of 1 was determined by interpretation of spectroscopic and spectrometric data from 1D and 2D NMR and HRESIMS experiments.

Highly oxygenated angucycline from Streptomyces sp. KCB15JA014.

LC/MS-based chemical screening of culture extract led to a new highly oxygenated angucycline derivative, grecocycline D (1), from Streptomyces sp. KCB15JA014, isolated from a soil sample of Oedolgae in Jeju Island, Korea. The planar structure was determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as HRESIMS and comparison with data from the literature.

Catenulisporidins A and B, 16-membered macrolides of the hygrolidin family produced by the chemically underexplored actinobacterium Catenulispora species.

Two new macrolide metabolites of the hygrolidin family, catenulisporidins A and B (1 and 2), together with a known compound hygrolidin (3), were isolated from the culture broth of the rare actinobacterium Catenulispora sp. KCB13F192. Their structures were elucidated on the basis of HRESIMS spectrometric and NMR spectroscopic analyses.

Isolation of new streptimidone derivatives, glutarimide antibiotics from Streptomyces sp. W3002 using LC-MS-guided screening.

A LC-MS-guided screening led to the isolation of two new streptimidone derivatives (2 and 3) containing a glutarimide ring and two glutarimide ring-opened compounds (4 and 5) along with a known glutarimide-containing polyketide, streptimidone (1) from Streptomyces sp. W3002 strain. Their structures were elucidated by MS and NMR spectroscopic analyses and by comparison with data from the literature.

Characterization of Gel16 as a Cytochrome P450 in Geldanamycin Biosynthesis and Analysis for an Endogenous Electron Transport System.

Geldanamycin and its derivatives, inhibitors of heat shock protein 90, are considered potent anticancer drugs, although their biosynthetic pathways have not yet been fully elucidated. The key step of conversion of 4,5-dihydrogeldanamycin to geldanamycin was expected to catalyze by a P450 monooxygenase, Gel16. The adequate bioconversions by cytochrome P450 mostly rely upon its interaction with redox partners.

Antibacterial Cyclic Lipopeptide Enamidonins with an Enamide-Linked Acyl Chain from a Streptomyces Species.

Three cyclic lipopeptides, including one known (1) and two new (2 and 3) compounds, that possess the rare enamide linkage group were discovered from Streptomyces sp. KCB14A132, an actinobacterium isolated from a soil sample collected from Jeung Island, Korea. The NMR and MS-based characterization showed that they differed in the amino acid residues in the peptide backbone.

Ulleungdin, a Lasso Peptide with Cancer Cell Migration Inhibitory Activity Discovered by the Genome Mining Approach.

The advances of genomic sequence analyses and genome mining tools have enabled the exploration of untapped microbial natural products. Through genome mining studies to discover cryptic natural products, we found biosynthetic genes encoding a new lasso peptide in the genome sequence of a soil bacterium, Streptomyces sp. KCB13F003 isolated from Ulleung Island (a small volcanic island), Korea.

Production of Bioactive 3'-Hydroxystilbene Compounds Using the Flavin-Dependent Monooxygenase Sam5.

The flavin-dependent monooxygenase Sam5 was previously reported to be a bifunctional hydroxylase with a coumarte 3-hydroxylase and a resveratrol 3'-hydroxylase activity. In this article, we showed the Sam5 enzyme has 3'-hydroxylation activities for methylated resveratrol (pinostilbene and pterostilbene), hydroxylated resveratrol (oxyresveratrol) and glycosylated resveratrol (piceid) as substrates. However, the use of piceid, a glycone type stilbene, as a substrate for bioconversion experiments with the Sam5 enzyme expressed in, does not convert to the hydroxylated compound astringin, but it has converted in vitro enzyme reactions.

Genomics-Driven Discovery of Chlorinated Cyclic Hexapeptides Ulleungmycins A and B from a Streptomyces Species.

Analysis of the genome sequence of Streptomyces sp. KCB13F003 showed the presence of a cryptic gene cluster encoding flavin-dependent halogenase and nonribosomal peptide synthetase. Pleiotropic approaches using multiple culture media followed by LC-MS-guided isolation and spectroscopic analysis enabled the identification of two new chlorinated cyclic hexapeptides, ulleungmycins A and B (1 and 2).