Identification and Proposed Relative and Absolute Configurations of Niphimycins C–E from the Marine-Derived <i>Streptomyces</i> sp. IMB7-145 by Genomic Analysis

Hu, Yuanyuan; Wang, Mian; Wu, Chunyan; Tan, Yi; Li, Jiao; Hao, Xiuhong; Duan, Yanbo; Guan, Yan; Shang, Xiao-Ya; Wang, Yiguang; Xiao, Chunling; Gan, Maoluo

doi:10.1021/acs.jnatprod.7b00859

Cited by 55 publications

(50 citation statements)

References 55 publications

(127 reference statements)

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“…Third, the substrate predictions of acyltransferase domains AT2, AT3, AT4, and AT8 are not accurate. Similar disagreements have occurred many times in structure prediction by other type I modular PKSs [6,22,23,24,25].…”

Section: Resultssupporting

confidence: 68%

Genome-Guided Discovery of Pretilactam from Actinosynnema pretiosum ATCC 31565

Wang

Sun

et al. 2019

Molecules

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Actinosynnema is a small but well-known genus of actinomycetes for production of ansamitocin, the payload component of antibody-drug conjugates against cancers. However, the secondary metabolite production profile of Actinosynnema pretiosum ATCC 31565, the most famous producer of ansamitocin, has never been fully explored. Our antiSMASH analysis of the genomic DNA of Actinosynnema pretiosum ATCC 31565 revealed a NRPS–PKS gene cluster for polyene macrolactam. The gene cluster is very similar to gene clusters for mirilactam and salinilactam, two 26-membered polyene macrolactams from Actinosynnema mirum and Salinispora tropica, respectively. Guided by this bioinformatics prediction, we characterized a novel 26-membered polyene macrolactam from Actinosynnema pretiosum ATCC 31565 and designated it pretilactam. The structure of pretilactam was elucidated by a comprehensive analysis of HRMS, 1D and 2D-NMR, with absolute configuration of chiral carbons predicted bioinformatically. Pretilactam features a dihydroxy tetrahydropyran moiety, and has a hexaene unit and a diene unit as its polyene system. A preliminary antibacterial assay indicated that pretilactam is inactive against Bacillus subtilis and Candida albicans.

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Section: Resultssupporting

confidence: 68%

Genome-Guided Discovery of Pretilactam from Actinosynnema pretiosum ATCC 31565

Wang

Sun

et al. 2019

Molecules

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“…Several other OTU sequences matched with over 85% identity to metabolites produced by Streptomyces, such as the recently discovered antibiotics niphimycins C-E [79] and the polyether ionophore antibiotic lasalocid [80], as well as the antifungal compound ibomycin [81]. [45].…”

Section: Metabolite/bgcs Tentatively Assigned To Ks Domainsmentioning

confidence: 99%

Diversity of Bacterial Biosynthetic Genes in Maritime Antarctica

et al. 2020

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Bacterial natural products (NPs) are still a major source of new drug leads. Polyketides (PKs) and non-ribosomal peptides (NRP) are two pharmaceutically important families of NPs and recent studies have revealed Antarctica to harbor endemic polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, likely to be involved in the production of novel metabolites. Despite this, the diversity of secondary metabolites genes in Antarctica is still poorly explored. In this study, a computational bioprospection approach was employed to study the diversity and identity of PKS and NRPS genes to one of the most biodiverse areas in maritime Antarctica-Maxwell Bay. Amplicon sequencing of soil samples targeting ketosynthase (KS) and adenylation (AD) domains of PKS and NRPS genes, respectively, revealed abundant and unexplored chemical diversity in this peninsula. About 20% of AD domain sequences were only distantly related to characterized biosynthetic genes. Several PKS and NRPS genes were found to be closely associated to recently described metabolites including those from uncultured and candidate phyla. The combination of new approaches in computational biology and new culture-dependent and -independent strategies is thus critical for the recovery of the potential novel chemistry encoded in Antarctica microorganisms. target the highly conserved ketosynthase (KS) and adenylation (AD) domains of PKS and NRPS genes, respectively. A growing number of studies have employed the PCR-based sequence tag approach to uncover PKS and NRPS gene diversity across different environmental microbiomes [7][8][9].Extreme environments, such as Antarctica, have the potential to reveal novel molecules since they are still a poorly explored source of chemical scaffolds and novel chemical diversity [10,11]. As such, metabarcoding approaches to study PKS and NRPS diversity in Antarctic ecosystems represent a simple and effective strategy to understand the biosynthetic potential of a large number of sampling sites [7]. A couple of such studies have been carried out very recently in Antarctica [12,13] revealing that soils at different Antarctica locations harbor multiple endemic PKS and NRPS genes, likely to be involved in the synthesis of new chemical diversity. In Antarctic soils, the percentage of yet-uncultured genera is expected to be much higher [14] than the 82% described for general soils [15]. A considerable fraction of such uncultured bacteria corresponds to members of the NP-rich Actinobacteria [16,17] and Cyanobacteria [18,19] phyla.King George Island is one of the largest ice-free and biodiverse areas in maritime Antarctica [20]. It harbors a high density of scientific stations, particularly in Maxwell Bay [21], where most of terrestrial biology research takes place. Although bacterial diversity studies have been conducted in this area [22,23], the diversity of bacterial biosynthetic genes has not been a target of study. Here, we perform a detailed study on soil samples from Maxwell Bay, with the main goal of assessing the...

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“…It was also isolated from other streptomycete strains [3][4][5], and has shown remarkable antibacterial and antifungal activities [2][3][4][5]. Simultaneously, many analogs such as guanidylfungins, amycins, shurimycins and niphimycins have been isolated from streptomycete strains [6][7][8][9]. The antimicrobial assays indicated that azalomycin F 5a , together with its derivatives, had remarkable anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activities [10].…”

Section: Introductionmentioning

confidence: 99%

Azalomycin F5a Eradicates Staphylococcus aureus Biofilm by Rapidly Penetrating and Subsequently Inducing Cell Lysis

Yuan

et al. 2020

IJMS

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Antimicrobial resistance has emerged as a serious threat to public health. Bacterial biofilm, as a natural lifestyle, is a major contributor to resistance to antimicrobials. Azalomycin F5a, a natural guanidine-containing polyhydroxy macrolide, has remarkable activities against Gram-positive bacteria, including Staphylococcus aureus, a major causative agent of hospital-acquired infections. To further evaluate its potential to be developed as a new antimicrobial agent, its influence on S. aureus biofilm formation was evaluated using the crystal violet method, and then its eradication effect against mature biofilms was determined by confocal laser scanning microscopy, the drop plate method, and regrowth experiments. The results showed that azalomycin F5a could significantly inhibit S. aureus biofilm formation, and such effects were concentration dependent. In addition, it can also eradicate S. aureus mature biofilms with the minimum biofilm eradication concentration of 32.0 μg/mL. As extracellular deoxyribonucleic acid (eDNA) plays important roles in the structural integrity of bacterial biofilm, its influence on the eDNA release in S. aureus biofilm was further analyzed using gel electrophoresis. Combined with our previous works, these results indicate that azalomycin F5a could rapidly penetrate biofilm and causes damages to the cell membrane, leading to an increase in DNase release and eventually eradicating S. aureus biofilm.

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Identification and Proposed Relative and Absolute Configurations of Niphimycins C–E from the Marine-Derived Streptomyces sp. IMB7-145 by Genomic Analysis

Cited by 55 publications

References 55 publications

Genome-Guided Discovery of Pretilactam from Actinosynnema pretiosum ATCC 31565

Genome-Guided Discovery of Pretilactam from Actinosynnema pretiosum ATCC 31565

Diversity of Bacterial Biosynthetic Genes in Maritime Antarctica

Azalomycin F5a Eradicates Staphylococcus aureus Biofilm by Rapidly Penetrating and Subsequently Inducing Cell Lysis

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