文献类型：期刊文献

英文题名：Green upcycling of tigogenin from sisal waste: Chemoenzymatic cascade synthesis of progesterone derivatives as an alternative to traditional steroid production processes

作者：Song, Lu[1];Luo, Zhi-Kun[1];He, Fu-Cheng[2];Huang, Lan-Ya[1];Xiong, Liang-Bin[2];Liu, Yong-Jun[1];Wei, Dong-Zhi[1];Wang, Feng-Qing[1]

机构：[1]East China Univ Sci & Technol, Newworld Inst Biotechnol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Shanghai Univ Med & Hlth Sci, Shanghai Key Lab Mol Imaging, Shanghai 201318, Peoples R China

年份：2026

卷号：531

外文期刊名：CHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20260720078249);WOS:【SCI-EXPANDED(收录号:WOS:001691942400001)】；

基金：This work was supported by the National Key Research and Development Program of China (2022YFA0912200) and the Shanghai Science and Technology Commission (24HC2820600) . We thank Professor Lian-Rong Wang for providing the S. lividans TK24-152 strain, which was engineered from S. lividans TK24 by incorporating the phosphorothioation-based phage defense system SspABCD-SspE [37] .

语种：英文

外文关键词：Tigogenin; Steroid pharmaceutical industry; Waste valorization; 3-keto-steroid-Delta(4)-dehydrogenase; 3-keto-steroid-Delta(1)-dehydrogenase

摘要：The structural properties of starting materials decisively govern industrial synthesis pathways for pharmaceutical steroids. Tigogenin, an economical and abundant byproduct from sisal fiber processing, exhibits substantial potential for steroid production. However, its industrial utility is limited by its saturated A-ring structure and environmentally detrimental application processes. To address these challenges, we developed an integrated chemoenzymatic pathway. First, tigogenin extracted from sisal residue was converted to 3 beta-hydroxy-5 alpha-pregnane-16-ene-20-one (3 beta-HP) via H2O2 degradation, a green alternative to Marker degradation. This was followed by efficient biotransformation to 5 alpha-pregnane-16-ene-3,20-dione (5 alpha-PD, >95% yield) using Streptomyces lividans TK24-152 instead of conventional Oppenauer oxidation, thereby eliminating toxic metal catalysts (CrO3 and aluminum tert-butoxide) in these traditional reaction processes. To selectively functionalize the A-ring of 5 alpha-PD, 3-ketosteroid-Delta(4)-dehydrogenase (Kst4D) and 3-ketosteroid-Delta(1)-dehydrogenase (Kst1D) were screened, engineered, and incorporated into S. lividans TK24-152. This generated strains (Rj4K, ReK3, and Rj4K-MnK2(A395G)) capable of converting 3 beta-HP via 5 alpha-PD to Delta(4,16(17))-diene-progesterone (4-PG), Delta(1,16(17))-diene-progesterone (1-PG), and Delta(1,4,16(17))-triene-progesterone (1,4-PG), respectively. To resolve bioavailability limitations of water-insoluble 3 beta-HP during scale-up, an emulsification system (3 beta-HP: Tween 80: HPCD = 10: 1: 20, w/w) was optimized. In 5 L fermenters, strains Rj4K and Rj4K-MnK2(A395G) demonstrated exceptional performance, achieving molar yields of 92.4% (from 20 g/L 3 beta-HP) and 82.2% (from 40 g/L 3 beta-HP) for 4-PG, and 86.7% (from 20 g/L 3 beta-HP) and 68.9% (from 40 g/L 3 beta-HP) for 1,4-PG. The overall tigogenin-to-product yields achieved 56.8-63.9% (for 4-PG) and 47.7-60.0% (for 1,4-PG), outperforming traditional diosgenin-based routes. In summary, this study establishes a sustainable chemoenzymatic strategy for steroid synthesis, enabling waste utilization while replacing hazardous reagents, with demonstrated industrial and environmental benefits.