Heterologous coexpression of Vitreoscilla hemoglobin and Bacillus megaterium glucanase in Streptomyces lydicus A02 enhanced its production of antifungal metabolites

Wu, Honglu; Li, Jinjin; Dong, Dan; Liu, Ting; Zhang, Taotao; Zhang, Dianpeng; Liu, Weicheng

doi:10.1016/j.enzmictec.2015.08.003

Cited by 8 publications

(3 citation statements)

References 38 publications

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“…Expression of the Vitreoscilla hemoglobin gene ( vgb ) has been shown to significantly improve growth, stress resistance and the production of recombinant proteins and valuable metabolites in many prokaryotic systems, primarily by increasing oxygen uptake and delivery. 170, 171 Consistent with studies demonstrating a positive correlation between antibiotic production levels and oxygen uptake, 172 heterologous vgb expression improved production of pimaricin in Streptomyces gilvosporeus and S. lydicus, 173, 174 actinorhodin in S. coelicolor, 175 and avermectin in S. avermitilis . 176 Expressing a different hemoprotein from Shinorhizobium meliloti has similar effects on metabolite production.…”

Section: Strategies For Strain Improvementsupporting

confidence: 75%

Engineering microbial hosts for production of bacterial natural products

et al. 2016

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Microbial fermentation provides as an attractive alternative to chemical synthesis for the production of structurally complex natural products. In most cases, however, production titers are low and need to be improved for compound characterization and/or commercial production. Owing to advances in functional genomics and genetic engineering technologies, microbial hosts can be engineered to overproduce a desired natural product, greatly accelerating the traditionally time-consuming strain improvement process. This review covers recent developments and challenges in the engineering of native and heterologous microbial hosts for production of bacterial natural products, focusing on the genetic tools and strategies for strain improvement. Special emphasis is placed on bioactive secondary metabolites from actinomycetes. The considerations for the choice of host systems will also be discussed in this review.

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Section: Strategies For Strain Improvementsupporting

confidence: 75%

Engineering microbial hosts for production of bacterial natural products

et al. 2016

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“…S1 ). We have constructed a series of engineered strains, including overexpression of the slnM gene with different promoters (ermEp* promoter, native promoter and dual promoters), heterologous expression of Vitreoscilla haemoglobin and coexpression of Vitreoscilla haemoglobin and Bacillus megaterium glucanase, to improve the natamycin yield or antifungal metabolites in strain A02 1 , 17 .…”

Section: Introductionmentioning

confidence: 99%

Comparative Genomic and Regulatory Analyses of Natamycin Production of Streptomyces lydicus A02

Wu¹,

Liu²,

Shi³

et al. 2017

Sci Rep

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Streptomyces lydicus A02 is used by industry because it has a higher natamycin-producing capacity than the reference strain S. natalensis ATCC 27448. We sequenced the complete genome of A02 using next-generation sequencing platforms, and to achieve better sequence coverage and genome assembly, we utilized single-molecule real-time (SMRT) sequencing. The assembled genome comprises a 9,307,519-bp linear chromosome with a GC content of 70.67%, and contained 8,888 predicted genes. Comparative genomics and natamycin biosynthetic gene cluster (BGC) analysis showed that BGC are highly conserved among evolutionarily diverse strains, and they also shared closer genome evolution compared with other Streptomyces species. Forty gene clusters were predicted to involve in the secondary metabolism of A02, and it was richly displayed in two-component signal transduction systems (TCS) in the genome, indicating a complex regulatory systems and high diversity of metabolites. Disruption of the phoP gene of the phoR-phoP TCS and nsdA gene confirmed phosphate sensitivity and global negative regulation of natamycin production. The genome sequence and analyses presented in this study provide an important molecular basis for research on natamycin production in Streptomyces, which could facilitate rational genome modification to improve the industrial use of A02.

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“…Previous studies have revealed that expression of VHb or its coexpression with other heterologous proteins increase the cell growth and production of antibiotics in a number of host organisms [21,22]. For instance, increased monensin production was observed by expressing VHb in S. cinnamonensis and heterologous co-expression of VHb and glucanase in S. ydicus A02 improved its natamycin production [23,24]. In the present study, we tested the effects of co-expressing VHb and key positive regulators of antibiotic biosynthesis on natamycin biosynthesis in S. gilvosporeus.…”

Section: Introductionmentioning

confidence: 99%

Enhanced natamycin production by co-expression of Vitreoscilla hemoglobin and antibiotic positive regulators in Streptomyces gilvosporeus

Wang

Sun

et al. 2018

Biotechnology & Biotechnological Equipment

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Natamycin, an important 26-member tetraene macrolide antifungal antibiotic, is widely used as antifungal agent in the food industry and medical fields. However, low yields of the currently used production strains limit its wider applications. To improve the productivity of natamycin-producing strains, we co-expressed the Vitreoscilla hemoglobin gene vgb in Streptomyces gilvosporeus with two genes that constitute part of the natamycin biosynthesis gene cluster: pimE (encoding a signalling protein) and pimM (encoding a positive regulator). Both genes were cloned and ligated into the shuttle vector pIMEP under the control of the strong, constitutive Perm promoter, and integrated into the chromosome of S. gilvosporeus via conjugation. Natamycin production was increased 40.3% upon overexpression of pimE and pimM. Furthermore, in order to alleviate oxygen limitation, we additionally expressed vgb in the pimE and pimM over-expressing strain, yielding S. gilvosporeus/pIMEP::pimE::pimM::vgb, which showed a further 55.7% improvement for natamycin production compared to that of the recipient strain. In conclusion, co-expression of pimE and pimM with vgb led to markedly increased natamycin production, thus pointing out a potential strategy for enhancing the microbial production of other antibiotics as well.

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Heterologous coexpression of Vitreoscilla hemoglobin and Bacillus megaterium glucanase in Streptomyces lydicus A02 enhanced its production of antifungal metabolites

Cited by 8 publications

References 38 publications

Engineering microbial hosts for production of bacterial natural products

Engineering microbial hosts for production of bacterial natural products

Comparative Genomic and Regulatory Analyses of Natamycin Production of Streptomyces lydicus A02

Enhanced natamycin production by co-expression of Vitreoscilla hemoglobin and antibiotic positive regulators in Streptomyces gilvosporeus

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