Genome-guided approaches and evaluation of the strategies to influence bioprocessing assisted morphological engineering of Streptomyces cell factories

Khushboo, .; Thakur, Mony; Kumar, Punit; Rajput, Deepanshi; Yadav, Vinod Kumar; Dhaka, Namrata; Shukla, Rishikesh; Dubey, Kashyap Kumar

doi:10.1016/j.biortech.2023.128836

Cited by 3 publications

(2 citation statements)

References 130 publications

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“…Indeed, the advancement of omics analysis technologies has greatly contributed to our comprehensive analysis of the high-yield mechanism ( Palazzotto et al, 2019 ; Wang et al, 2020 ). For example, by employing genomics, we can sequence and analyze the entire genetic makeup of a strain, uncovering crucial genetic variations that influence the production of specific natural products ( Liu et al, 2021 ; Khushboo et al, 2023 ). Transcriptomics allows us to study gene expression patterns under various conditions, shedding light on which genes are upregulated or downregulated during natural product biosynthesis ( Zhang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insight for improving butenyl-spinosyn production through combined ARTP/UV mutagenesis and ribosome engineering in Saccharopolyspora pogona

Zhao,

Hussain,

Mohsin

et al. 2024

Front. Bioeng. Biotechnol.

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Butenyl-spinosyn is a highly effective, wide-spectrum and environmentally-friendly biological insecticide produced by Saccharopolyspora pogona. However, its scale-up is impeded due to its lower titer in wild-type strains. In this work, ARTP/UV mutagenesis and ribosome engineering were employed to enhance the butenyl-spinosyn production, and a stable mutant Saccharopolyspora pogona aG6 with high butenyl-spinosyn yield was successfully obtained. For the first time, the fermentation results in the 5 L bioreactor demonstrated that the butenyl-spinosyn produced by mutant Saccharopolyspora pogona aG6 reached the maximum value of 130 mg/L, almost 4-fold increase over the wild-type strain WT. Furthermore, comparative genomic, transcriptome and target metabolomic analysis revealed that the accumulation of butenyl-spinosyn was promoted by alterations in ribosomal proteins, branched-chain amino acid degradation and oxidative phosphorylation. Conclusively, the proposed model of ribosome engineering combined with ARTP/UV showed the improved biosynthesis regulation of butenyl-spinosyn in S. pogona.

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Section: Introductionmentioning

confidence: 99%

Mechanistic insight for improving butenyl-spinosyn production through combined ARTP/UV mutagenesis and ribosome engineering in Saccharopolyspora pogona

Zhao,

Hussain,

Mohsin

et al. 2024

Front. Bioeng. Biotechnol.

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“…Nevertheless, the total regulatory networks might be more complex than we expect. For example, it has been found that cell morphology significantly affects the production of natural products ( Khushboo et al, 2023 ). Moreover, target deciphering of the regulatory mechanisms for a certain BGC is highly technology-dependent and time-consuming.…”

Section: Introductionmentioning

confidence: 99%

Development of a native-locus dual reporter system for the efficient screening of the hyper-production of natural products in Streptomyces

Zhou

Zhao

et al. 2023

Front. Bioeng. Biotechnol.

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Streptomyces is renowned for its abundant production of bioactive secondary metabolites, but most of these natural products are produced in low yields. Traditional rational network refactoring is highly dependent on the comprehensive understanding of regulatory mechanisms and multiple manipulations of genome editing. Though random mutagenesis is fairly straightforward, it lacks a general and effective strategy for high throughput screening of the desired strains. Here in an antibiotic daptomycin producer S. roseosporus, we developed a dual-reporter system at the native locus of the daptomycin gene cluster. After elimination of three enzymes that potentially produce pigments by genome editing, a gene idgS encoding the indigoidine synthetase and a kanamycin resistant gene neo were integrated before and after the non-ribosomal peptidyl synthetase genes for daptomycin biosynthesis, respectively. After condition optimization of UV-induced mutagenesis, strains with hyper-resistance to kanamycin along with over-production of indigoidine were efficiently obtained after one round of mutagenesis and target screening based on the dual selection of the reporter system. Four mutant strains showed increased production of daptomycin from 1.4 to 6.4 folds, and significantly improved expression of the gene cluster. Our native-locus dual reporter system is efficient for targeting screening after random mutagenesis and would be widely applicable for the effective engineering of Streptomyces species and hyper-production of these invaluable natural products for pharmaceutical development.

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Multi-steps microfiltration of micelles from fermentation of Streptomyces tsukubaensis and its impact on proteins retention and tacrolimus yield

Bertan,

Cremasco

2024

Food and Bioproducts Processing

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Genome-guided approaches and evaluation of the strategies to influence bioprocessing assisted morphological engineering of Streptomyces cell factories

Cited by 3 publications

References 130 publications

Mechanistic insight for improving butenyl-spinosyn production through combined ARTP/UV mutagenesis and ribosome engineering in Saccharopolyspora pogona

Mechanistic insight for improving butenyl-spinosyn production through combined ARTP/UV mutagenesis and ribosome engineering in Saccharopolyspora pogona

Development of a native-locus dual reporter system for the efficient screening of the hyper-production of natural products in Streptomyces

Multi-steps microfiltration of micelles from fermentation of Streptomyces tsukubaensis and its impact on proteins retention and tacrolimus yield

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