| Summary: | 4′-N-demethyl-vicenistatin is a vicenistatin analogue that has better antitumor activity with promising applications in the pharmaceuticals industry. The harnessing of the complete potential of this compound necessitates a systematic optimization of the culture medium to enable the cost-effective production of 4′-N-demethyl-vicenistatin by <i>Streptomyces parvus</i> SCSIO Mla-L010/Δ<i>vicG</i>. Therefore, in this study, a sequential approach was employed to screen the significant medium compositions, as follows: one-factor-at-a-time (OFAT) and Plackett–Burman designs (PBD) were initially utilized. Cassava starch, glycerol, and seawater salt were identified as the pivotal components influencing 4′-N-demethyl-vicenistatin production. To further investigate the direct and interactive effects of these key components, a three-factor, five-level central composite design (CCD) was implemented. Finally, response surface methodology (RSM) and an artificial-neural-network-genetic-algorithm (ANN-GA) were employed for the modeling and optimization of the medium components to enhance efficient 4′-N-demethyl-vicenistatin production. The ANN-GA model showed superior reliability, achieving the most 4′-N-demethyl-vicenistatin, at 0.1921 g/L, which was 17% and 283% higher than the RSM-optimized and initial medium approaches, respectively. This study represents pioneering work on statistically guided optimization strategies for enhancing 4′-N-demethyl-vicenistatin production through medium optimization.
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