A screen for strains producing 11α,17α-dihydroxy progesterone and optimization of fermentation conditions
Corticosteroids are widely used in clinical practice.11α,17α-dihydroxy progesterone serves as a crucial intermediate in corticosteroid synthesis.The prevailing biological method for its preparation involves microbial biosynthesis using 17α-hydroxy progesterone as a substrate.However,achieving efficient production of 11 α,17α-dihydroxy progesterone using progesterone as substrate is more cost-effective.We screened our laboratory library for strains capable of modifying progesterone,and found Gibberella intermedia CA3-1to proficient in utilizing progesterone.HPLC,MS,and NMR analyses confirmed that the product was indeed 11α,17α-dihydroxy progesterone.We subsequently optimized fermentation medium components through single-factor experiments and orthogonal experiments to determine the optimal composition:lactose(25 g/L),yeast powder(15 g/L),Fe2(SO4)3(0.4 g/L),and corn steep liquor(15 g/L).With a substrate feeding amount of 0.5 g/L and a 72 h fermentation time,we achieved a substrate conversion rate of 82.2％and a final concentration of 11α,17α-dihydroxy progesterone of 43.5 mg/L compared to the pre-optimization concentration of 30.2 mg/L representing a significant 44％improvement.We successfully identified a novel strain capable of hydroxylating progesterone through effective screening methods,and enhanced its yield of 11α,17α-dihydroxy progesterone by optimizing the fermentation medium using single-factor and orthogonal testing.This discovery offers a promising approach for the industrial production of 11α,17α-dihydroxy progesterone.
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