Enhancement of 9α-Hydroxy-4-androstene-3,17-dione Production from Soybean Phytosterols by Deficiency of a Regulated Intramembrane Proteolysis Metalloprotease in Mycobacterium neoaurum,Journal of Agricultural and Food Chemistry

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Enhancement of 9α-Hydroxy-4-androstene-3,17-dione Production from Soybean Phytosterols by Deficiency of a Regulated Intramembrane Proteolysis Metalloprotease in Mycobacterium neoaurum
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2017-11-28 00:00:00 , DOI: 10.1021/acs.jafc.7b03766
Liang-Bin Xiong ₁ , Wan-Ju Sun ₁ , Yong-Jun Liu ₁ , Feng-Qing Wang ₁ , Dong-Zhi Wei ₁

Affiliation

Modification of the sterol catabolism pathway in mycobacteria may result in the accumulation of some valuable steroid pharmaceutical intermediates, such as 9α-hydroxy-4-androstene-3,17-dione (9-OHAD). In previous work, sigma factor D (SigD) was identified as a negative factor of the 9-OHAD production in Mycobacterium neoaurum. Here, the deficiency of rip1 putatively coding for a regulated intramembrane proteolysis metalloprotease (Rip1), which could cleave the negative regulator of SigD (anti-SigD), enhanced the transcription of some key genes (choM1, kshA, and hsd4A) in the sterol catabolic pathway. Furthermore, the deletion of rip1 increased the consumption of phytosterols by 37.8% after 96 h of growth in M. neoaurum. The production of 9-OHAD in the engineered M. neoaurumΔkstD1ΔkstD2ΔkstD3Δrip1 (MnΔk123Δrip1) strain was ultimately increased by 27.3% compared to that in its parental strain M. neoaurumΔkstD1ΔkstD2ΔkstD3 (MnΔk123). This study further confirms the important role of SigD-related factors in the catabolism of sterols.

中文翻译：

新分枝杆菌中膜内蛋白水解金属蛋白酶的缺乏促进大豆植物甾醇生产9α-羟基-4-雄烷3,17-二酮的作用

分枝杆菌中固醇分解代谢途径的修饰可能导致某些有价值的类固醇药物中间体的积累，例如9α-羟基-4-雄烯-3,17-二酮（9-OHAD）。在以前的工作中，西格玛因子D（SigD）被确定为新分枝杆菌中9-OHAD产生的负因子。在这里，rip1的缺陷可能编码了膜内蛋白水解金属蛋白酶（Rip1），它可以切割SigD的负调控子（anti-SigD），增强了固醇中一些关键基因（choM1，kshA和hsd4A）的转录。分解代谢途径。此外，rip1的删除在新分支杆菌生长96小时后，植物固醇的消耗增加了37.8％。在该工程生产9- OHAD的M. neoaurum Δ kstD1 Δ kstD2 Δ kstD3 Δ RIP1（MnΔ K123 Δ RIP1）菌株最终增加了27.3％相比，在其亲本株M. neoaurum Δ kstD1 Δ kstD2 Δ kstD3（ MnΔ K123）。这项研究进一步证实了SigD相关因子在固醇分解代谢中的重要作用。

更新日期：2017-11-28

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