In this paper, fermentation dynamics process of Streptomyces aureochromogenes was researched. The production of polyoxins in culture medium with moderate concentration sucrose was at a relative high level. And, when the carbon source changed to glucose, the mycelium grew in a better condition, while no poloxins was produced. This phenomenon also happened when increasing the initial concentration of sucrose to three times. To evaluate the regulatory mechanism of polyoxin production, comparative proteomic analysis of S. aureochromogenes was conducted. The result showed that tricarboxylic acid cycle (TCA) cycle, amino metabolism, and fatty acid metabolism were active and glycolysis was repressed. And, the fact that stress and stress-related protein like superoxide dismutase (SOD), Clp protease, and catalase were highly expressed indicated a higher regulator level in synthesis of polyoxins. In addition, enzymes related to transcription or translation processes also revealed a correlation between specific cell growth rate and polyoxin production. This study will be helpful in better understanding the biosynthesis mechanism of polyoxins and metabolism regulation in this process.