Complete Genome Sequence of Streptomyces clavuligerus F613-1, an Industrial Producer of Clavulanic Acid

Cao, Guangxiang; Zhong, Chunlong; Zong, Guanghua; Fu, Jiafang; Liu, Zhong; Zhang, Guimin; Qin, Ronghuo

doi:10.1128/genomea.01020-16

Cited by 14 publications

(17 citation statements)

References 7 publications

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“…The genome of the strain F613-1 has been sequenced and assembled (Cao et al 2016). Genome annotation was previously performed as recommended by the NCBI (National Center for Biotechnology Information) online pipeline for prokaryotic species.…”

Section: Genome Annotation and Analysismentioning

confidence: 99%

“…Streptomyces clavuligerus strain F613-1 is an important industrial producer with high clavulanic acid production, but poor ability to produce 5S clavam compounds, and its complete genome of F613-1 has been sequenced (Cao et al 2016). In this study, we analyzed the compact genome sequence of F613-1, which contains a 6.78 Mb chromosome, considerably smaller than other reported S. clavuligerus genomes, and a 707 Kb pSCL4-like plasmid (smaller than 1.8 Mb pSCL4, however, carrying the intact paralog gene cluster related with biosynthesis of clavulanic acid).…”

Section: Introductionmentioning

confidence: 99%

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Impacts of horizontal gene transfer on the compact genome of the clavulanic acid-producing Streptomyces strain F613-1

Zhao

Zhong

et al. 2018

3 Biotech

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Mobile genetic elements involved in mediating horizontal transfer events contribute to bacterial evolution, and bacterial genomic plasticity and instability result in variation in functional genetic information in Streptomyces secondary metabolism. In a previous study, we reported the complete genome sequence of the industrial Streptomyces strain F613-1, which produces high yields of clavulanic acid. In this study, we used comparative genomics and bioinformatics to investigate the unique genomic features of this strain. Taken together, comparative genomics were used to systematically investigate secondary metabolism capabilities and indicated that frequent exchange of genetic materials between Streptomyces replicons may shape the remarkable diversities in their secondary metabolite repertoires. Moreover, a 136.9-kb giant region of plasticity (RGP) was found in the F613-1 chromosome, and the chromosome and plasmid pSCL4 are densely packed with an exceptionally large variety of potential secondary metabolic gene clusters, involving several determinants putatively accounting for antibiotic production. In addition, the differences in the architecture and size of plasmid pSCL4 between F613-1 and ATCC 27064 suggest that the pSCL4 plasmid could evolve from pSCL4-like and pSCL2-like extrachromosomal replicons. Furthermore, the genomic analyses revealed that strain F613-1 has developed specific genomic architectures and genetic patterns that are well suited to meet the requirements of industrial innovation processes.

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Section: Genome Annotation and Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impacts of horizontal gene transfer on the compact genome of the clavulanic acid-producing Streptomyces strain F613-1

Zhao

Zhong

et al. 2018

3 Biotech

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“…Streptomyces clavuligerus F613-1 is an industrial CA producer, and its complete genome sequence has been reported (Cao et al, 2016). The putative TCS CagRS is located near the CA biosynthetic gene cluster in F613-1 (Figure 1C).…”

Section: Resultsmentioning

confidence: 99%

“…TCSs not only respond to changes in environmental factors, but in Streptomyces , also influence development and secondary metabolism such as antibiotic production (Mendes et al, 2007). S. clavuligerus F613-1 is an industrial CA producer strain, and we have previously reported the complete genome sequence of this strain (Cao et al, 2016). In this study, we identified TCS CagRS, which is annotated as orf22/orf23 in S. clavuligerus 27064 (Song et al, 2009) and which is close to the CA biosynthetic gene cluster in F613-1.…”

Section: Introductionmentioning

confidence: 99%

The CagRS Two-Component System Regulates Clavulanic Acid Metabolism via Multiple Pathways in Streptomyces clavuligerus F613-1

Qin

Zong

et al. 2019

Front. Microbiol.

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Streptomyces clavuligerus F613-1 produces a clinically important β-lactamase inhibitor, clavulanic acid (CA). Although the biosynthesis pathway of CA has essentially been elucidated, the global regulatory mechanisms of CA biosynthesis remain unclear. The paired genes cagS and cagR , which are annotated, respectively, as orf22 and orf23 in S. clavuligerus ATCC 27064, encode a bacterial two-component regulatory system (TCS) and were found next to the CA biosynthetic gene cluster of S. clavuligerus F613-1. To further elucidate the regulatory mechanism of CA biosynthesis, the CagRS TCS was deleted from S. clavuligerus F613-1. Deletion of cagRS resulted in decreased production of CA, but the strain phenotype was not otherwise affected. Both transcriptome and ChIP-seq data revealed that, in addition to CA biosynthesis, the CagRS TCS mainly regulates genes involved in primary metabolism, such as glyceraldehyde 3-phosphate (G3P) metabolism and arginine biosynthesis. Notably, both G3P and arginine are precursors of CA. Electrophoretic mobility shift assays demonstrated that the response regulator CagR could bind to the intergenic regions of argG, argC, oat1, oat2, ceaS1 , and claR in vitro , suggesting that CagR can directly regulate genes involved in arginine and CA biosynthesis. This study indicated that CagRS is a pleiotropic regulator that can directly affect the biosynthesis of CA and indirectly affect CA production by regulating the metabolism of arginine and G3P. Our findings provide new insights into the regulation of CA biosynthetic pathways and provide an innovative approach for future metabolic engineering efforts for CA production in S. clavuligerus .

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“…These plasmids can recombine with the chromosome, enhancing the genetic interchange of secondary metabolites (Medema et al, ). Interestingly, S. cattleya NRRL 3841 and S. lipmannii NRRL 3584 are two species of the genus lacking plasmids (Netolitzky, Wu, Jensen, & Roy, ), and even the strain S. clavuligerus F613‐1 has a different number of plasmids (Cao et al, ). These findings suggest that plasmids could provide a vehicle for genetic interchange by horizontal gene transfer or some other mechanism in this species and even in the genus.…”

Section: Introductionmentioning

confidence: 99%

A putative antimicrobial peptide from Hymenoptera in the megaplasmid pSCL4 of Streptomyces clavuligerus ATCC 27064 reveals a singular case of horizontal gene transfer with potential applications

Ayala-Ruano

Santander-Gordón

Tejera

et al. 2019

Ecology and Evolution

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Streptomyces clavuligerus is a Gram‐positive bacterium that is a high producer of secondary metabolites with industrial applications. The production of antibiotics such as clavulanic acid or cephamycin has been extensively studied in this species; nevertheless, other aspects, such as evolution or ecology, have received less attention. Furthermore, genes that arise from ancient events of lateral transfer have been demonstrated to be implicated in important functions of host species. This approximation discovered relevant genes that genomic analyses overlooked. Thus, we studied the impact of horizontal gene transfer in the S. clavuligerus genome. To perform this task, we applied whole‐genome analysis to identify a laterally transferred sequence from different domains. The most relevant result was a putative antimicrobial peptide (AMP) with a clear origin in the Hymenoptera order of insects. Next, we determined that two copies of these genes were present in the megaplasmid pSCL4 but absent in the S. clavuligerus ATCC 27064 chromosome. Additionally, we found that these sequences were exclusive to the ATCC 27064 strain (and so were not present in any other bacteria) and we also verified the expression of the genes using RNAseq data. Next, we used several AMP predictors to validate the original annotation extracted from Hymenoptera sequences and explored the possibility that these proteins had post‐translational modifications using peptidase cleavage prediction. We suggest that Hymenoptera AMP‐like proteins of S. clavuligerus ATCC 27064 may be useful for both species adaptation and as an antimicrobial molecule with industrial applications.

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Complete Genome Sequence of Streptomyces clavuligerus F613-1, an Industrial Producer of Clavulanic Acid

Cited by 14 publications

References 7 publications

Impacts of horizontal gene transfer on the compact genome of the clavulanic acid-producing Streptomyces strain F613-1

Impacts of horizontal gene transfer on the compact genome of the clavulanic acid-producing Streptomyces strain F613-1

The CagRS Two-Component System Regulates Clavulanic Acid Metabolism via Multiple Pathways in Streptomyces clavuligerus F613-1

A putative antimicrobial peptide from Hymenoptera in the megaplasmid pSCL4 of Streptomyces clavuligerus ATCC 27064 reveals a singular case of horizontal gene transfer with potential applications

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