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Efficient Production of 9,22-Dihydroxy-23,24-bisnorchol-4-ene-3-one from Phytosterols by Modifying Multiple Genes in Mycobacterium fortuitum.
Han, Suwan; Liu, Xiangcen; He, Beiru; Zhai, Xinghui; Yuan, Chenyang; Li, Yixin; Lin, Weichao; Wang, Haoyu; Zhang, Baoguo.
  • Han S; Laboratory of Biorefinery, Shanghai Advanced Research Institute, Chinese Academy of Sciences, No. 99 Haike Road, Pudong, Shanghai 201210, China.
  • Liu X; University of Chinese Academy of Sciences, Beijing 100049, China.
  • He B; Laboratory of Biorefinery, Shanghai Advanced Research Institute, Chinese Academy of Sciences, No. 99 Haike Road, Pudong, Shanghai 201210, China.
  • Zhai X; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Yuan C; Laboratory of Biorefinery, Shanghai Advanced Research Institute, Chinese Academy of Sciences, No. 99 Haike Road, Pudong, Shanghai 201210, China.
  • Li Y; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Lin W; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  • Wang H; Laboratory of Biorefinery, Shanghai Advanced Research Institute, Chinese Academy of Sciences, No. 99 Haike Road, Pudong, Shanghai 201210, China.
  • Zhang B; University of Chinese Academy of Sciences, Beijing 100049, China.
Int J Mol Sci ; 25(7)2024 Mar 22.
Article en En | MEDLINE | ID: mdl-38612391
ABSTRACT
C19 steroids and C22 steroids are vital intermediates for the synthesis of steroid drugs. Compared with C19 steroids, C22 steroids are more suitable for synthesizing progesterone and adrenocortical hormones, albeit less developed. 9,22-dihydroxy-23,24-bisnorchol-4-ene-3-one(9-OHBA), due to its substituents at positions C-9 and C-22, is a beneficial and innovative steroid derivative for synthesizing corticosteroids. We focused on the C22 pathway in Mycobacterium fortuitum ATCC 35855, aiming to develop a productive strain that produces 9-OHBA. We used a mutant strain, MFΔkstD, that knocked out kstds from Mycobacterium fortuitum ATCC 35855 named MFKD in this study as the original strain. Hsd4A and FadA5 are key enzymes in controlling the C19 metabolic pathway of steroids in Mycobacterium fortuitum ATCC 35855. After knocking out hsd4A, MFKDΔhsd4A accumulated 81.47% 9-OHBA compared with 4.13% 9-OHBA in the strain MFKD. The double mutant MFKDΔhsd4AΔfadA5 further improved the selectivity of 9-OHBA to 95.13%, and 9α-hydroxy-4-androstenedione (9-OHAD) decreased to 0.90% from 4.19%. In the end, we obtained 6.81 g/L 9-OHBA from 10 g/L phytosterols with a molar yield of 80.33%, which showed the best performance compared with formerly reported strains.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fitosteroles / Mycobacterium fortuitum Idioma: En Año: 2024 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fitosteroles / Mycobacterium fortuitum Idioma: En Año: 2024 Tipo del documento: Article