Genomewide Transcriptome Responses of Arthrobacter simplex to Cortisone Acetate and its Mutants with Enhanced Δ1‑Dehydrogenation Efficiency

Due to its superior Δ1-dehydrogenation ability, Arthrobacter simplex has been widely used for the biotransformation of cortisone acetate (CA) into prednisone acetate (PA) in the steroid industry. However, its molecular fundamentals are still unclear. Herein, the genome organization, gene regulation, and previously unreported genes involved in Δ1-dehydrogenation are revealed through genome and transcriptome analysis. A comparative study of transcriptomes of an industrial strain induced by CA or at different biotransformation periods was performed. By overexpression, the roles of six genes in CA conversion were confirmed, among which sufC and hsaA behaved better by reinforcing catalytic enzyme activity and substrate transmembrane transport. Additionally, GroEL endowed cells with the strongest stress tolerance by alleviating oxidative damage and enhancing energy levels. Finally, an optimal strain was created by coexpressing three genes, achieving 46.8 and 70.6% increase in PA amount and productivity compared to the initial values, respectively. Our study expanded the understanding of the Δ1-dehydrogenation mechanism and offered an effective approach for excellent steroid-transforming strains.