GlnR‐mediated regulation of KstR controls cholesterol catabolism in <i>Mycobacterium smegmatis</i>

Ma, Haiyan; Liu, Weibing; Zhang, Xiao-Peng; Hu, Hao-Qi; Gu, Sheng-Di; Yuan, Hao; Ye, Bang‐Ce

doi:10.1002/bab.2197

Cited by 2 publications

(1 citation statement)

References 22 publications

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“…It directly controls the transcription of over 100 genes involved in crucial nitrogen stress survival processes, such as nitrate and urea utilization and the use of cellular components as a source of ammonium (Jenkins et al, 2013). Moreover, GlnR controls redox sensing and lipid anabolism through WhiB3 (You et al, 2019) and controls cholesterol catabolism through KstR (Ma et al, 2022). M. smegmatis also has another global nitrogen regulator, AmtR, whose expression is controlled by a cis-encoded small RNA (Petridis et al, 2016) and competes with GlnR to regulate urea metabolism.…”

Section: In Mycobacteriamentioning

confidence: 99%

Research progress on GlnR-mediated regulation in Actinomycetes

Gao,

Li,

et al. 2023

Front. Microbiol.

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This review constitutes a summary of current knowledge on GlnR, a global regulator, that assumes a critical function in the regulation of nitrogen metabolism of Actinomycetes. In cross-regulation with other regulators, GlnR was also shown to play a role in the regulation of carbon and phosphate metabolisms as well as of secondary metabolism. A description of the structure of the GlnR protein and of its binding sites in various genes promoters regions is also provided. This review thus provides a global understanding of the critical function played by GlnR in the regulation of primary and secondary metabolism in Actinomycetes.

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Section: In Mycobacteriamentioning

confidence: 99%

Research progress on GlnR-mediated regulation in Actinomycetes

Gao,

Li,

et al. 2023

Front. Microbiol.

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Rerouting phytosterol degradation pathway for directed androst-1,4-diene-3,17-dione microbial bioconversion

Ke,

Cui,

Ren

et al. 2024

Appl Microbiol Biotechnol

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Steroid-based drugs are now mainly produced by the microbial transformation of phytosterol, and a two-step bioprocess is adopted to reach high space–time yields, but byproducts are frequently observed during the bioprocessing. In this study, the catabolic switch between the C19- and C22-steroidal subpathways was investigated in resting cells of Mycobacterium neoaurum NRRL B-3805, and a dose-dependent transcriptional response toward the induction of phytosterol with increased concentrations was found in the putative node enzymes including ChoM2, KstD1, OpccR, Sal, and Hsd4A. Aldolase Sal presented a dominant role in the C22 steroidal side-chain cleavage, and the byproduct was eliminated after sequential deletion of opccR and sal. Meanwhile, the molar yield of androst-1,4-diene-3,17-dione (ADD) was increased from 59.4 to 71.3%. With the regard of insufficient activity of rate-limiting enzymes may also cause byproduct accumulation, a chromosomal integration platform for target gene overexpression was established supported by a strong promoter L2 combined with site-specific recombination in the engineered cell. Rate-limiting steps of ADD bioconversion were further characterized and overcome. Overexpression of the kstD1 gene further strengthened the bioconversion from AD to ADD. After subsequential optimization of the bioconversion system, the directed biotransformation route was developed and allowed up to 82.0% molar yield with a space–time yield of 4.22 g·L−1·day−1. The catabolic diversion elements and the genetic overexpression tools as confirmed and developed in present study offer new ideas of M. neoaurum cell factory development for directed biotransformation for C19- and C22-steroidal drug intermediates from phytosterol. Key points • Resting cells exhibited a catabolic switch between the C19- and C22-steroidal subpathways. • The C22-steroidal byproduct was eliminated after sequential deletion of opccR and sal. • Rate-limiting steps were overcome by promoter engineering and chromosomal integration.

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GlnR‐mediated regulation of KstR controls cholesterol catabolism in Mycobacterium smegmatis

Cited by 2 publications

References 22 publications

Research progress on GlnR-mediated regulation in Actinomycetes

Research progress on GlnR-mediated regulation in Actinomycetes

Rerouting phytosterol degradation pathway for directed androst-1,4-diene-3,17-dione microbial bioconversion

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