Progress in Understanding the Genetic Information and Biosynthetic Pathways behind <i>Amycolatopsis</i> Antibiotics, with Implications for the Continued Discovery of Novel Drugs

Su, Chen; Wu, Qihao; Shen, Qingqing; Wang, Hong

doi:10.1002/cbic.201500542

Cited by 30 publications

(36 citation statements)

References 82 publications

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“…The genomic studies have revealed that Amycolatopsis have comparatively large genomes *5 Mb (A. halophila YIM93223-10) to 10.86 Mb (A. balhimycina FH 1894), circular chromosomes and contains over 20 secondary metabolic gene clusters. As these bacteria are mostly soil dwellers, they experience a diverse and changing habitat which may benefit from a larger repertoire of genes allowing the organism to acclimatize and adapt to the changing conditions [17]. The occurrence of indigenous plasmids in this genus is also not very common.…”

Section: General Features Of the Genus Amycolatopsismentioning

confidence: 99%

Genetics and Genomics of the Genus Amycolatopsis

2016

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Actinobacteria are gram-positive filamentous bacteria which contains some of the most deadly human pathogens (Mycobacterium tuberculosis, M. leprae, Corynebacterium diphtheriae, Nocardia farcinica), plant pathogens (Streptomyces scabies, Leifsonia xyli) along with organisms that produces antibiotic (Streptomycetes, Amycolatopsis, Salinospora). Interestingly, these bacteria are equipped with an extraordinary capability of producing antibiotics and other metabolites which have medicinal properties. With the advent of inexpensive genome sequencing techniques and their clinical importance, many genomes of Actinobacteria have been successfully sequenced. These days, with the constant increasing number of drug-resistant bacteria, the urgent need for discovering new antibiotics has emerged as a major scientific challenge. And, unfortunately the traditional method of screening bacterial strains for the production of antibiotics has decreased leading to a paradigm shift in the planning and execution of discovery of novel biosynthetic gene clusters via genome mining process. The entire focus has shifted to the evaluation of genetic capacity of organisms for metabolite production and activation of cryptic gene clusters. This has been made possible only due to the availability of genome sequencing and has been augmented by genomic studies and new biotechnological approaches. Through this article, we present the analysis of the genomes of species belonging to the genus Amycolatopsis, sequenced till date with a focus on completely sequenced genomes and their application for further studies.

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Section: General Features Of the Genus Amycolatopsismentioning

confidence: 99%

Genetics and Genomics of the Genus Amycolatopsis

2016

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“…The genus Amycolatopsis is well known for the commercial production of multiple antibiotics, including the important broad spectrum antibiotics rifamycin and, vancomycin ( Xu et al, 2014 ; Chen et al, 2016 ). These strains also have the potential to produce a number of other secondary metabolites and bioactive molecules ( Adamek et al, 2018 ) and, can be exploited for a range of biotechnological applications ( Davila Costa and Amoroso, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Revisiting the Taxonomic Status of the Biomedically and Industrially Important Genus Amycolatopsis, Using a Phylogenomic Approach

et al. 2018

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Strains belonging to the genus Amycolatopsis are well known for the production of a number of important antimicrobials and other bioactive molecules. In this study, we have sequenced the genomes of five Amycolatopsis strains including Amycolatopsis circi DSM 45561T, Amycolatopsis palatopharyngis DSM 44832T and Amycolatopsis thermalba NRRL B-24845T. The genome sequences were analyzed with 52 other publically available Amycolatopsis genomes, representing 34 species, and 12 representatives from related genera including Saccharomonospora, Saccharopolyspora, Saccharothrix, Pseudonocardia and Thermobispora. Based on the core genome phylogeny, Amycolatopsis strains were subdivided into four major clades and several singletons. The genus Amycolatopsis is homogeneous with only three strains noted to group with other genera. Amycolatopsis halophila YIM93223T is quite distinct from other Amycolatopsis strains, both phylogenetically and taxonomically, and belongs to a distinct genus. In addition, Amycolatopsis palatopharyngis DSM 44832T and Amycolatopsis marina CGMCC4 3568T grouped in a clade with Saccharomonospora strains and showed similar taxogenomic differences to this genus as well as other Amycolatopsis strains. The study found a number of strains, particularly those identified as Amycolatopsis orientalis, whose incorrect identification could be resolved by taxogenomic analyses. Similarly, some unclassified strains could be assigned with species designations. The genome sequences of some strains that were independently sequenced by different laboratories were almost identical (99–100% average nucleotide and amino acid identities) consistent with them being the same strain, and confirming the reproducibility and robustness of genomic data. These analyses further demonstrate that whole genome sequencing can reliably resolve intra- and, inter-generic structures and should be incorporated into prokaryotic systematics.

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“…Within the actinomycetes, the genus Streptomyces is the most prolific and most studied producer of secondary metabolites, but members of the families Pseudonocardiaceae and Micromonosporaceae have also shown to produce a broad diversity of bioactive molecules. Among Pseudonocardiaceae , members of the genus Amycolatopsis produce several relevant secondary metabolites, such as balhimycin, vancomycin, avoparcin, ristomycin, chelocardin, chloroeremomycin, ECO-0501 and rifamycin (Chen et al, 2016 ; Kumari et al, 2016 ). More recently, other antibiotics have been described from some Amycolatopsis strains such as macrotermycins A–D (Beemelmanns et al, 2017 ), pargamicins B–D (Hashizume et al, 2017 ) and rifamorpholines A–E (Xiao et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative Genomics and Biosynthetic Potential Analysis of Two Lichen-Isolated Amycolatopsis Strains

et al. 2018

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Actinomycetes have been extensively exploited as one of the most prolific secondary metabolite-producer sources and continue to be in the focus of interest in the constant search of novel bioactive compounds. The availability of less expensive next generation genome sequencing techniques has not only confirmed the extraordinary richness and broad distribution of silent natural product biosynthetic gene clusters among these bacterial genomes, but also has allowed the incorporation of genomics in bacterial taxonomy and systematics. As part of our efforts to isolate novel strains from unique environments, we explored lichen-associated microbial communities as unique assemblages to be studied as potential sources of novel bioactive natural products with application in biotechnology and drug discovery. In this work, we have studied the whole genome sequences of two new Amycolatopsis strains (CA-126428 and CA-128772) isolated from tropical lichens, and performed a comparative genomic analysis with 41 publicly available Amycolatopsis genomes. This work has not only permitted to infer and discuss their taxonomic position on the basis of the different phylogenetic approaches used, but has also allowed to assess the richness and uniqueness of the biosynthetic pathways associated to primary and secondary metabolism, and to provide a first insight on the potential role of these bacteria in the lichen-associated microbial community.

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Progress in Understanding the Genetic Information and Biosynthetic Pathways behind Amycolatopsis Antibiotics, with Implications for the Continued Discovery of Novel Drugs

Cited by 30 publications

References 82 publications

Genetics and Genomics of the Genus Amycolatopsis

Genetics and Genomics of the Genus Amycolatopsis

Revisiting the Taxonomic Status of the Biomedically and Industrially Important Genus Amycolatopsis, Using a Phylogenomic Approach

Comparative Genomics and Biosynthetic Potential Analysis of Two Lichen-Isolated Amycolatopsis Strains

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