Glycopeptide Antibiotics: Genetics, Chemistry, and New Screening Approaches

Yushchuk, Oleksandr; Ostash, Bohdan

doi:10.1007/978-981-16-6132-7_16

Cited by 6 publications

(4 citation statements)

References 126 publications

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“…随着 GPA 不断被发掘与鉴定, K. C. Nicolaou 等根据结构骨架组成与修饰的差异于 1999 年提出将 GPA 分为五个亚型: I-V 型 [6,47] (图 2). 彼时所发掘的 GPA 均为七肽骨架, 因而在分型时将 GPA 肽骨架的氨基酸从氨基端至羧基端顺序标注为 1 至 7 位, 即 AA1-AA2-AA3-AA4-AA5-AA6-AA7.…”

Section: 糖肽抗生素的分类unclassified

“…I-V 型 GPA 中典型的结构特征着以红色突出显示 Figure 2 Classification of glycopeptide antibiotics: characteristic structural differences among Type I-V GPAs are shown in red. (3)糖苷后修饰 [47,50] . 负责 GPA 前体与糖苷合成、糖苷后修饰、转运、抗性以及调控的基因通常在放线菌的染色体上成簇排列, 形成 GPA 生物合成基因簇.…”

Section: 糖肽抗生素的分类unclassified

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糖肽抗生素天然产物研究进展

Guo,

Li,

Deng

et al. 2024

Sci. Sin.-Vitae

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Section: 糖肽抗生素的分类unclassified

糖肽抗生素天然产物研究进展

Guo,

Li,

Deng

et al. 2024

Sci. Sin.-Vitae

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“…Many other natural and semisynthetic GPAs are known but they are not clinically used [20,26]. Although every known GPA BGC carries a gene for an StrR-like PSR [27], the most studied are bbr (from the balhimycin BGC in Amycolatopsis balhimycina DSM 5908) [28][29][30], tei15* from the teicoplanin BGC (tei) [31][32][33], and dbv4 from the A40926 BGC (dbv) [30,34,35]. All these genes appear to encode key activators of GPA biosynthesis, and their knocking out resulted in the complete abolishment of antibiotic production [32,35].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Heterologous Regulatory Genes from Lipodepsipeptide Biosynthetic Gene Clusters on the Production of Teicoplanin and A40926

Zhukrovska,

Binda,

Fedorenko

et al. 2024

Antibiotics

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StrR-like pathway-specific transcriptional regulators (PSRs) function as activators in the biosynthesis of various antibiotics, including glycopeptides (GPAs), aminoglycosides, aminocoumarins, and ramoplanin-like lipodepsipeptides (LDPs). In particular, the roles of StrR-like PSRs have been previously investigated in the biosynthesis of streptomycin, novobiocin, GPAs like balhimycin, teicoplanin, and A40926, as well as LDP enduracidin. In the current study, we focused on StrR-like PSRs from the ramoplanin biosynthetic gene cluster (BGC) in Actinoplanes ramoplaninifer ATCC 33076 (Ramo5) and the chersinamycin BGC in Micromonospora chersina DSM 44151 (Chers28). Through the analysis of the amino acid sequences of Ramo5 and Chers28, we discovered that these proteins are phylogenetically distant from other experimentally investigated StrR PSRs, although all StrR-like PSRs found in BGCs for different antibiotics share a conserved secondary structure. To investigate whether Ramo5 and Chers28, given their phylogenetic positions, might influence the biosynthesis of other antibiotic pathways governed by StrR-like PSRs, the corresponding genes (ramo5 and chers28) were heterologously expressed in Actinoplanes teichomyceticus NRRL B-16726 and Nonomuraea gerenzanensis ATCC 39727, which produce the clinically-relevant GPAs teicoplanin and A40926, respectively. Recombinant strains of NRRL B-16726 and ATCC 39727 expressing chers28 exhibited improved antibiotic production, although the expression of ramo5 did not yield the same effect. These results demonstrate that some StrR-like PSRs can “cross-talk” between distant biosynthetic pathways and might be utilized as tools for the activation of silent BGCs regulated by StrR-like PSRs.

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“…Genes encoding these pathways are co-localized, co-expressed, and organized in large biosynthetic gene clusters (BGCs). Dalbaheptide biosynthesis has been extensively studied and reviewed in recent years [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Occurrence of vanHAX and Related Genes beyond the Actinobacteria Phylum

Yushchuk

Binda

Fedorenko

et al. 2022

Genes

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Clinically relevant glycopeptide antibiotics remain among the most successful classes of natural antibacterials. This success, however, is endangered by the spread of glycopeptide resistance genes, also known as van genes. Thus, it is important to trace and comprehend possible routes of van gene dissemination. In the current work, we present a comprehensive bioinformatic analysis aimed at mapping the occurrence of van genes beyond the Actinobacteria phylum—the most likely natural reservoir of van genes. We show that two additional classes of Gram-positive bacteria, Erysipelotrichia and Ktedonobacteria, as well as one class of Gram-negative bacteria, Anaerolineae, carry van genes. Additionally, we demonstrate that various new genera belonging to the classes Clostridia and Bacilli also carry van genes. The majority of discovered van loci are co-localized with MGE-related genes of various types. Finally, we propose a phylogeny-based scenario for the spread of van genes, unraveling a network of consequential horizontal gene transfer events linking the phylum Actinobacteria with the five other bacterial classes carrying van genes.

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Glycopeptide Antibiotics: Genetics, Chemistry, and New Screening Approaches

Cited by 6 publications

References 126 publications

糖肽抗生素天然产物研究进展

糖肽抗生素天然产物研究进展

The Impact of Heterologous Regulatory Genes from Lipodepsipeptide Biosynthetic Gene Clusters on the Production of Teicoplanin and A40926

Occurrence of vanHAX and Related Genes beyond the Actinobacteria Phylum

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