Metabolic Engineering of Filamentous Actinomycetes

Beck, Charlotte; Blin, Kai; Gren, Tetiana; Jiang, Xinglin; Mohite, Omkar S.; Palazzotto, Emilia; Tong, Yaojun; Charusanti, Pep; Weber, Tilmann

doi:10.1002/9783527823468.ch17

Cited by 1 publication

(1 citation statement)

References 193 publications

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“…However, the majority of these BGCs, are silent when tested under standard laboratory conditions ( Liu et al, 2021 ). Therefore, numerous strategies, including heterologous expression ( Kang and Kim, 2021 ), overexpression in native host ( Li H. et al, 2022 ), promoter engineering ( Liu X. F. et al, 2022 ), transcriptional regulation engineering ( Li et al, 2019 ; Martínez-Burgo et al, 2019 ) and ribosome engineering ( Zhang et al, 2019 ; Li et al, 2021 ) have been developed to activate these BGCs in NP discovery studies ( Beck et al, 2021 ; Liu et al, 2021 ). However, since most of these studies focused on one or more metabolites, the full potential of Streptomyces has rarely been studied.…”

Section: Introductionmentioning

confidence: 99%

Metabolic perturbation of Streptomyces albulus by introducing NADP-dependent glyceraldehyde 3-phosphate dehydrogenase

Mao,

Zhang,

Dai

et al. 2024

Front. Microbiol.

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The available resources of Streptomyces represent a valuable repository of bioactive natural products that warrant exploration. Streptomyces albulus is primarily utilized in the industrial synthesis of ε-poly-L-lysine (ε-PL). In this study, the NADP-dependent glyceraldehyde 3-phosphate dehydrogenase (GapN) from Streptococcus mutans was heterologously expressed in S. albulus CICC11022, leading to elevated intracellular NADPH levels and reduced NADH and ATP concentrations. The resulting perturbation of S. albulus metabolism was comprehensively analyzed using transcriptomic and metabolomic methodologies. A decrease in production of ε-PL was observed. The expression of gapN significantly impacted on 23 gene clusters responsible for the biosynthesis of secondary metabolites. A comprehensive analysis revealed a total of 21 metabolites exhibiting elevated levels both intracellularly and extracellularly in the gapN expressing strain compared to those in the control strain. These findings underscore the potential of S. albulus to generate diverse bioactive natural products, thus offering valuable insights for the utilization of known Streptomyces resources through genetic manipulation.

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