Cephalosporin is a β-lactam antibiotic produced by Acremonium chrysogenum using submerged fermentation. Carbon and nitrogen are the most influential medium ingredients for cephalosporin formation. The purpose of this study was to obtain the best composition of media for cephalosporin C production. Response surface methodology was used for production optimization. The results showed that molasses of 70 g/Lwas the best carbon source, while the best nitrogen source was the combination of corn steep liquor, urea and ammonium sulphate. DL-methionine, carbon, and nitrogen source significantly affected the production of cephalosporin C. The mathematically modelled optimization showed that the highest production of cephalosporin C (3876 mg/L) was obtained using medium composition of 68.28 g/L molasses, 71.61 g/L nitrogen, and 0.4 g/L DL-methionine. Laboratory verification using the same medium composition produced 3696 mg/L of cephalosporin C, being 4.65% different from the mathematically optimized results. Medium optimization increased the cephalosprin C production which was 1.48 times higher than that using the previous medium, where the maximum production was only 2487 mg / L.Keywords: Carbon, cephalosporin C, cultivation medium, nitrogen, A. chrysogenum ABSTRAKSefalosporin C adalah golongan antibiotik β-lactam yang dihasilkan Acremonium chrysogenum melalui fermentasi cair. Komponen yang sangat berpengaruh terhadap produksi sefalosporin C adalah sumber karbon dan nitrogen. Penelitian ini bertujuan mendapatkan komposisi media terbaik untuk produksi sefalosporin C. Optimasi dilakukan menggunakan metode respon permukaan. Hasil menunjukkan bahwa molases 70 g/L adalah sumber karbon terbaik dan kombinasi corn steep liquor, urea dan ammonium sulfat adalah sumber nitrogen terbaik. DL-methionin, sumber karbon, dan nitrogen berpengaruh nyata terhadap produksi sefalosporin C. Optimasi menggunakan model matematika menunjukkan produksi sefalosporin C tertinggi (3876 mg/L) yang diperoleh dengan komposisi media 68,28 g/L molases, 71,61 g/L nitrogen, dan 0,4 g/L DL-methionin. Verfikasi di laboratorium menggunakan komposisi media yang sama menghasilkan sefalosporin C sebesar 3696 mg/L, berbeda 4,65% dibanding dengan hasil optimasi matematis. Optimasi media mampu meningkatkan produksi sefalosprin C sebesar 1,48 kali dibanding media yang digunakan sebelumnya, dimana maksimal hanya menghasilkan 2487 mg/L.Kata kunci: Karbon, sefalosporin C, media kultivasi, nitrogen, A. chrysogenum
Enhancement of Cephalosporin C production by cultivation of Cephalosporium acremonium M25 using a mixture of inocula
