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Keywords = non-core metabolic pathway of steroids

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23 pages, 2299 KB  
Review
New Insights into the Modification of the Non-Core Metabolic Pathway of Steroids in Mycolicibacterium and the Application of Fermentation Biotechnology in C-19 Steroid Production
by Yang Zhang, Peiyao Xiao, Delong Pan and Xiuling Zhou
Int. J. Mol. Sci. 2023, 24(6), 5236; https://doi.org/10.3390/ijms24065236 - 9 Mar 2023
Cited by 9 | Viewed by 3603
Abstract
Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD), and 9α-hydroxy-4-androstene-3,17-dione (9-OHAD), which belong to C-19 steroids, are critical steroid-based drug intermediates. The biotransformation of phytosterols into C-19 steroids by Mycolicibacterium cell factories is the core step in the synthesis of steroid-based drugs. The production performance of engineered [...] Read more.
Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD), and 9α-hydroxy-4-androstene-3,17-dione (9-OHAD), which belong to C-19 steroids, are critical steroid-based drug intermediates. The biotransformation of phytosterols into C-19 steroids by Mycolicibacterium cell factories is the core step in the synthesis of steroid-based drugs. The production performance of engineered mycolicibacterial strains has been effectively enhanced by sterol core metabolic modification. In recent years, research on the non-core metabolic pathway of steroids (NCMS) in mycolicibacterial strains has made significant progress. This review discusses the molecular mechanisms and metabolic modifications of NCMS for accelerating sterol uptake, regulating coenzyme I balance, promoting propionyl-CoA metabolism, reducing reactive oxygen species, and regulating energy metabolism. In addition, the recent applications of biotechnology in steroid intermediate production are summarized and compared, and the future development trend of NCMS research is discussed. This review provides powerful theoretical support for metabolic regulation in the biotransformation of phytosterols. Full article
(This article belongs to the Special Issue Microbial Enzymes and Metabolites)
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15 pages, 826 KB  
Article
AKR1C1 as a Biomarker for Differentiating the Biological Effects of Combustible from Non-Combustible Tobacco Products
by Sangsoon Woo, Hong Gao, David Henderson, Wolfgang Zacharias, Gang Liu, Quynh T. Tran and G.L. Prasad
Genes 2017, 8(5), 132; https://doi.org/10.3390/genes8050132 - 3 May 2017
Cited by 16 | Viewed by 5578
Abstract
Smoking has been established as a major risk factor for developing oral squamous cell carcinoma (OSCC), but less attention has been paid to the effects of smokeless tobacco products. Our objective is to identify potential biomarkers to distinguish the biological effects of combustible [...] Read more.
Smoking has been established as a major risk factor for developing oral squamous cell carcinoma (OSCC), but less attention has been paid to the effects of smokeless tobacco products. Our objective is to identify potential biomarkers to distinguish the biological effects of combustible tobacco products from those of non-combustible ones using oral cell lines. Normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines were exposed to different tobacco product preparations (TPPs) including cigarette smoke total particulate matter (TPM), whole-smoke conditioned media (WS-CM), smokeless tobacco extract in complete artificial saliva (STE), or nicotine (NIC) alone. We performed microarray-based gene expression profiling and found 3456 probe sets from 101A, 1432 probe sets from 101B, and 2717 probe sets from HGEC to be differentially expressed. Gene Set Enrichment Analysis (GSEA) revealed xenobiotic metabolism and steroid biosynthesis were the top two pathways that were upregulated by combustible but not by non-combustible TPPs. Notably, aldo-keto reductase genes, AKR1C1 and AKR1C2, were the core genes in the top enriched pathways and were statistically upregulated more than eight-fold by combustible TPPs. Quantitative real time polymerase chain reaction (qRT-PCR) results statistically support AKR1C1 as a potential biomarker for differentiating the biological effects of combustible from non-combustible tobacco products. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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