Abstract Ikarugamycin is a member of the polycyclic tetramate macrolactams (PTMs) family natural products with diverse biological activities. The biochemical mechanisms for formation ring systems in PTMs remain elusive. enzymatic mechanism constructing an inner five‐membered ikarugamycin reported. A three‐gene‐cassette ikaABC from marine‐derived Streptomyces sp. ZJ306 sufficient conferring production heterologous host. IkaC catalyzes reductive cyclization reaction to form by Michael...

We report the activation of a PTM gene cluster in marine-derived <italic>Streptomyces pactum</italic>, leading to discovery six new PTMs, pactamides A-F.

A nonribosomal peptide synthetase (NRPS) gene cluster (sfa) was identified in Streptomyces thioluteus to direct the biosynthesis of diisonitrile antibiotic SF2768. Its biosynthetic pathway reasonably proposed based on bioinformatics analysis, metabolic profiles mutants, and elucidation intermediate shunt product structures. Bioinformatics-based alignment found a putative ATP-binding cassette (ABC) transporter related iron import within cluster, which implied that might be siderophore....

Xiamycin A (XMA) and oxiamycin (OXM) are bacterial indolosesquiterpenes featuring rare pentacyclic ring systems isolated from a marine-derived Streptomyces sp. SCSIO 02999. The putative biosynthetic gene cluster for XMA/OXM was identified by partial genome sequencing approach. Eighteen genes were proposed to be involved in biosynthesis, including five terpene synthesis via non-mevalonate pathway, eight encoding oxidoreductases, regulation resistance. Targeted disruptions of 13 within the xia...

The biosynthesis gene cluster (fls) for atypical angucycline fluostatins was identified from the marine derived Micromonospora rosaria SCSIO N160 and confirmed by knockouts biochemical characterization of a bifunctional oxygenase FlsO2. absolute configuration key biosynthetic intermediate prejadomycin determined first time Cu Kα X-ray analysis. Heterologous expression intact fls-gene in Streptomyces coelicolor YF11 presence 3% sea salts led to isolation two new compounds: fluostatin L (1)...

Abstract Microbes can enter into healthy plants as endophytes and confer beneficial functions. The entry of commensal microbes involves penetrating plant defense. Most mechanisms about overcoming defense are focused on adapted pathogens, while the mechanism involved in endophyte evades to achieve harmonious commensalism is unclear. Here, we discover a that an bacterium Bacillus subtilis BSn5 reduce stimulate defensive response by producing lantibiotic subtilomycin bind self-produced...

Abstract Lomaiviticin A and difluostatin are benzofluorene-containing aromatic polyketides in the atypical angucycline family. Although these dimeric compounds potent antitumor agents, how nature constructs their complex structures remains poorly understood. Herein, we report discovery of a number fluostatin type with varied C−C C−N coupling patterns. We also demonstrate that dimers not true secondary metabolites, but instead derived from non-enzymatic deacylation biosynthetic acyl...

Permian lithium-rich karstic bauxites are newly discovered in central Yunnan province, western margin of the South China Block, with a reserve 16 million tonnes, which has great potential for aluminum and lithium exploitation. Provenance ore-forming processes still debatable. Mineralogical, geochemical, geochronological analyses were conducted on two typical bauxite profiles to explore genetic process province. Profile A contains three layers from bottom top: clayey bauxite, claystone,...

Cinnamoyl-containing nonribosomal peptides (CCNPs) constitute a unique family of natural products. The enzyme mechanism for the biaryl phenol coupling reaction bicyclic CCNPs remains unclear. Herein, we report discovery two new arabinofuranosylated cihanmycins (CHMs) A (1) and B (2) from Amycolatopsis cihanbeyliensis DSM 45679 identification CHM biosynthetic gene cluster (cih BGC) by heterologous expression in Streptomyces lividans SBT18 to afford CHMs C (3) D (4). structure 1 was confirmed...

A known polycyclic tetramate macrolactam (aburatubolactam C, 3) and three new ones (aburatubolactams D–F, 4–6, respectively) were isolated from the marine-derived Streptomyces sp. SCSIO 40070. The absolute configuration of 3 was established by X-ray analysis. combinatorial biosynthetic approach unveiled enzymes dictating formation distinct 5/5-type ring systems (such as C7–C14 cyclization AtlB1 in 5 C6–C13 AtlB2 6) aburatubolactams.

The strain SCSIO N160 was isolated from a South China Sea sediment sample and characterized as Micromonospora rosaria species on the basis of its 16S rRNA gene sequence. Three new fluostatins, I-K (1-3), were culture M. N160, together with six known compounds, fluostatins C-F (4-7), rabelomycin (8), phenanthroviridone (9). structure fluostatin D (5) confirmed by an X-ray crystallographic study. absolute configuration 1 3 assigned electronic circular dichroism calculations. Compounds 8 9...

The biosynthetic gene cluster for caerulomycin A (1) was cloned and characterized from the marine actinomycete Actinoalloteichus cyanogriseus WH1-2216-6, which revealed an unusual hybrid polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) system. crmL disruption mutant accumulated L (2) with extended l-leucine at C-7, implicating amidohydrolase activity CrmL. leucine-removing confirmed crude CrmL enzymes. Heterologous expression of 1 led to production in Streptomyces coelicolor.

A 92 kb silent hybrid polyketide and nonribosomal peptide gene cluster in marine-derived Streptomyces pactum SCSIO 02999 was activated by genetically manipulating the regulatory genes, including knockout of two negative regulators (totR5 totR3) overexpression a positive regulator totR1, to direct production known totopotensamides (TPMs) (1) B (3) novel sulfonate-containing analogue TPM C (2). Inactivation totG led accumulation lacking glycosyl moiety, which indicated TotG as dedicated...

Xanthone-containing natural products display diverse pharmacological properties. The biosynthetic mechanisms of the xanthone formation have not been well documented. Here we show that flavoprotein monooxygenase FlsO1 in biosynthesis fluostatins only functionally compensates for FlsO2 converting prejadomycin to dehydrorabelomycin, but also unexpectedly converts xanthone-containing by catalyzing three successive oxidations including hydroxylation, epoxidation and Baeyer-Villiger oxidation. We...

Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been rich source of biologically active compounds. Two new (

The immunosuppressive agent caerulomycin A features a unique 2,2'-bipyridine core structure and an unusual oxime functionality. Genetic biochemical evidence confirms that the formation in biosynthesis is catalyzed by CrmH, flavin-dependent two-component monooxygenase compatible with multiple flavin reductases, from primary amine via N-hydroxylamine intermediate. Structure homologue-guided site-directed mutagenesis studies identify four amino acid residues are essential for CrmH catalysis....

The P450 enzyme XiaM was identified as a candidate to form the C-24 carboxyl group in xiamycin A (1). Alteration of medium composition led discovery four new compounds from ΔxiaM and ΔxiaK (encoding an aromatic ring hydroxylase) mutants. Biotransformation experiments revealed that capable converting methyl through diol aldehyde intermediates.

The identification of a lobophorin biosynthetic gene cluster from the deep-sea derived Streptomyces sp. SCSIO 01127 reveals paradigm three glycosyltransferases (GTs) LobG1–LobG3 being responsible for appending four sugars. Characterization five differentially glycosylated metabolites GT gene-inactivation mutants allowed assignment functions and implication LobG3 as an iterative to attach two digitoxoses.

Three new macrolactams, heronamides D–F (1–3), were isolated from the deep-sea-derived Streptomyces sp. SCSIO 03032 upon changing cultivation conditions. The planar structures of (1–3) elucidated by extensive MS and NMR spectroscopic analyses comparisons with closely related A–C. relative configurations 1–3 deduced detailed analysis 3JHH values NOESY data. absolute 1 2 determined chemical modifications application modified Mosher's method. None compounds exhibited obvious antimicrobial or...

Heronamides belong to a growing family of β-amino acid polyketide macrolactams (βPMs) with an unsaturated side chain. The biosynthetic gene cluster for heronamide F was identified from the deep-sea-derived Streptomyces sp. SCSIO 03032. involvement in biosynthesis confirmed by functional characterization P450 enzyme HerO as 8-hydroxylase tailoring biosynthesis. presence migrated double bonds conjugated diene-containing chain heronamides feeding experiments labeled small carboxylic molecules....

Flavoenzymes are ubiquitous in biological systems and catalyze a diverse range of chemical transformations.

Abstract Meroterpenoids of the ochraceopones family featuring a linear tetracyclic scaffold exhibit exceptional antiviral and anti‐inflammatory activities. The biosynthetic pathway chemical logic to generate this tetracycle, however, remain unknown. In study, we identified characterized all enzymes afford elucidated complete pathway. We demonstrated that was derived from an angular precursor. A multifunctional cytochrome P450 OchH validated catalyze free‐radical‐initiated carbon‐carbon bond...

Mangrove derived actinomycetes are a rich reservoir of bioactive natural products and play important roles in pharmaceutical chemistry. In screen from mangrove rhizosphere sedimental environments, the isolated strain