Nattokinase is able to hydrolyze fibri oriented fibers, reducing blood pressure to the arteries and heart valves. People use nattokinase enzyme through ingestion by natto food or functional food to dissolve blood clots. In fermentation by Bacillus subtilis natto, the bacterium can generate this enzyme. The optimized culture medium has 6 factors such as glucose, soybean peptone, K2HPO4, MgSO4, NaCl, CaCl2 and the rate of these in medium is identified by response furface methodology (RSM) and central composite design (CCD). The highest nattokinase yield was 69.3
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