Investigation of Penicillin Binding Protein (PBP)-like Peptide Cyclase and Hydrolase in Surugamide Non-ribosomal Peptide Biosynthesis

Zhou, Yongjun; Xiao, Lin; Xu, Chunmin; Shen, Yaoyao; Wang, Shuping; Liao, Hongze; Li, Lei; Deng, Hai; Lin, Hou‐Wen

doi:10.1016/j.chembiol.2019.02.010

Cited by 32 publications

(39 citation statements)

References 31 publications

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“…The non-ribosome polypeptide synthase is responsible for the synthesis of peptide secondary metabolites, such as surugamides and ferricrocin [45,46]. In C. arbuscula, 12 putative NRPS genes were found.…”

Section: Other Sm Clusters For Mycotoxin Biosynthesismentioning

confidence: 99%

Genomic and transcriptomic survey of an endophytic fungus Calcarisporium arbuscula NRRL 3705 and potential overview of its secondary metabolites

et al. 2020

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Background: Secondary metabolites as natural products from endophytic fungi are important sources of pharmaceuticals. However, there is currently little understanding of endophytic fungi at the omics levels about their potential in secondary metabolites. Calcarisporium arbuscula, an endophytic fungus from the fruit bodies of Russulaceae, produces a variety of secondary metabolites with anti-cancer, anti-nematode and antibiotic activities. A comprehensive survey of the genome and transcriptome of this endophytic fungus will help to understand its capacity to biosynthesize secondary metabolites and will lay the foundation for the development of this precious resource. Results: In this study, we reported the high-quality genome sequence of C. arbuscula NRRL 3705 based on Single Molecule Real-Time sequencing technology. The genome of this fungus is over 45 Mb in size, larger than other typical filamentous fungi, and comprises 10,001 predicted genes, encoding at least 762 secretory-proteins, 386 carbohydrate-active enzymes and 177 P450 enzymes. 398 virulence factors and 228 genes related to pathogen-host interactions were also predicted in this fungus. Moreover, 65 secondary metabolite biosynthetic gene clusters were revealed, including the gene cluster for the mycotoxin aurovertins. In addition, several gene clusters were predicted to produce mycotoxins, including aflatoxin, alternariol, destruxin, citrinin and isoflavipucine. Notably, two independent gene clusters were shown that are potentially involved in the biosynthesis of alternariol. Furthermore, RNA-Seq assays showed that only expression of the aurovertin gene cluster is much stronger than expression of the housekeeping genes under laboratory conditions, consistent with the observation that aurovertins are the predominant metabolites. Gene expression of the remaining 64 gene clusters for compound backbone biosynthesis was all lower than expression of the housekeeping genes, which partially explained poor production of other secondary metabolites in this fungus. Conclusions: Our omics data, along with bioinformatics analysis, indicated that C. arbuscula NRRL 3705 contains a large number of biosynthetic gene clusters and has a huge potential to produce a profound number of secondary metabolites. This work also provides the basis for development of endophytic fungi as a new resource of natural products with promising biological activities.

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Section: Other Sm Clusters For Mycotoxin Biosynthesismentioning

confidence: 99%

Genomic and transcriptomic survey of an endophytic fungus Calcarisporium arbuscula NRRL 3705 and potential overview of its secondary metabolites

et al. 2020

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“…However, the cpp cluster also lacks a TE domain to release and cyclize the pentapeptides but contains a PBP-like stand-alone protein (cppA) that may be involved in the release and cyclization of the peptide chains of both BE-18257 antibiotics and pentaminomycins, as it was proposed by Kaweevan (2020) and Hwang (2020). In fact, it has been recently described that SurE, a standalone enzyme belonging to the PBP family, is involved in the release and macrocyclization of two different surugamides (B and F) encoded in a single gene cluster (Matsuda et al, 2019a;2019b;Zhou et al, 2019).…”

Section: Identification Of the Cpp Gene Cluster From The Whole Genomementioning

confidence: 99%

“…The proposed cluster harbors regulatory, transport-related and biosynthetic genes, including cytochromes P450 and two NRPS, each of them predicted to synthesize one type of pentapeptide. The cluster lacks any gene harboring a thioesterase (TE) domain but contains a stand-alone enzyme belonging to the Penicillin Binding Protein (PBP) family, that, likewise to what has been demonstrated for SurE in the biosynthesis of surugamide (Matsuda et al, 2019a;2019b;Zhou et al, 2019), is proposed to act as a trans-acting TE cyclizing both BE-18257 A-B and pentaminomycins C-E (Kaweewan et al, 2020;Hwang et al, 2020).…”

mentioning

confidence: 99%

One pathway, two cyclic pentapeptides: heterologous expression of BE-18257 A-C and pentaminomycins A-E fromStreptomyces cacaoiCA-170360

Román‐Hurtado

Sánchez‐Hidalgo

Martín

et al. 2020

Preprint

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The strain Streptomyces cacaoi CA-170360 produces the cyclic pentapeptides pentaminomycins A-E and BE-18257 A-C, two families of cyclopeptides synthesized by two nonribosomal peptide synthetases encoded in tandem within the same biosynthetic gene cluster. In this work, we have cloned and confirmed the heterologous expression of this biosynthetic gene cluster, demonstrating that each of the nonribosomal peptide synthetases present in the cluster is involved in the biosynthesis of each group of cyclopeptides. In addition, we discuss the involvement of a stand-alone enzyme belonging to the Penicillin Binding Protein family in the release and macrocyclization of the peptides.

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“…The non-ribosome polypeptide synthase is responsible for the synthesis of peptide secondary metabolites, such as surugamides and ferricrocin [48,49]. In C. arbuscula, 12 putative NRPS genes were found.…”

Section: Other Sm Clusters For Mycotoxin Biosynthesismentioning

confidence: 99%

Genomic and transcriptomic survey of an endophytic fungus Calcarisporium arbuscula NRRL 3705 and potential overview of its secondary metabolites

Cheng

Cao

Chen

et al. 2019

Preprint

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Endophytic fungi can produce many active secondary metabolites, which are important resources of natural medicines. However, there is currently little understanding of endophytic fungi at the omics levels. Calcarisporium arbuscula , an endophytic fungus from the healthy fruit of russulaceae, can produce a variety of secondary metabolites with anti-cancer, anti-nematode and antibiotic bioactivities. Comprehensive survey of the endophytic fungi genome and transcriptome will help to understand their capacity to biosynthesize secondary metabolites and lay the foundation for the development of these precious resources. In this study，we reported the high-quality genome sequence of a strain C. arbuscula NRRL 3705 based on Single Molecule Real-Time sequencing technology. The genome of this fungus is over 45 Mb in size, relatively larger than other typical filamentous fungi, and comprises 10,001 predictable genes, encoding at least 762 secretory-proteins, 386 carbohydrate-active enzymes and 177 P450 enzymes. 398 virulence factors and 228 genes related to pathogen-host interactions were also predicted in this fungus. Moreover , 65 secondary metabolite biosynthetic gene clusters were revealed, including the gene cluster for mycotoxins aurovertins. In addition, several gene clusters were predicted to produce various mycotoxins, including aflatoxin, alternariol, destruxin, citrinin and isoflavipucine. Notably, two independent gene clusters were shown possibly involved in the biosynthesis of alternariol. Furthermore, RNA-Seq assay showed that only the expression of aurovertin gene cluster is much stronger than the housekeeping genes under laboratory conditions, consistent with that aurovertins are the predominant metabolites. The gene expression of the remaining 64 gene clusters for compound backbone biosynthesis was all lower than the housekeeping genes, which might partially explain poor production of other secondary metabolites in this fungus.Our omics data along with bioinformatics analysis indicated that C. arbuscula NRRL 3705 contains a large number of biosynthetic gene clusters and has a huge potential to produce profound secondary metabolites. This work also provides the basis for development of endophytic fungi as a new resource of natural products with promising biological activities.

show abstract

Investigation of Penicillin Binding Protein (PBP)-like Peptide Cyclase and Hydrolase in Surugamide Non-ribosomal Peptide Biosynthesis

Cited by 32 publications

References 31 publications

Genomic and transcriptomic survey of an endophytic fungus Calcarisporium arbuscula NRRL 3705 and potential overview of its secondary metabolites

Genomic and transcriptomic survey of an endophytic fungus Calcarisporium arbuscula NRRL 3705 and potential overview of its secondary metabolites

One pathway, two cyclic pentapeptides: heterologous expression of BE-18257 A-C and pentaminomycins A-E fromStreptomyces cacaoiCA-170360

Genomic and transcriptomic survey of an endophytic fungus Calcarisporium arbuscula NRRL 3705 and potential overview of its secondary metabolites

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