Dewi, Diana (2026) Peningkatan Produksi Borrelidin Oleh Streptomyces Rochei Untuk Pengembangan Obat Antimalaria: Seleksi Koloni, Optimasi Media Dan Peningkatan Skala Fermentasi. Doctoral thesis, Institut Teknologi Sepuluh Nopember.
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Abstract
Borrelidin merupakan senyawa makrolida dengan berbagai bioaktivitas, termasuk aktivitas antimalaria dengan IC₅₀ 0,9 ng/L, akan tetapi memiliki toksisitas tinggi terhadap sel MRC-5 (IC₅₀ 410 nM). Senyawa ini potensial dikembangkan sebagai kandidat obat antimalaria baru melalui modifikasi struktur kimia dengan menurunkan toksisitasnya. Pengembangan kandidat obat memerlukan ketersediaan borrelidin dalam jumlah besar, sementara yield fermentasi oleh Streptomyces rochei masih rendah. Penelitian ini bertujuan meningkatkan produktivitas borrelidin oleh endofit S. rochei yang diisolasi dari tanaman obat Lempuyang melalui seleksi koloni, optimasi media, dan peningkatan skala fermentasi pada bioreaktor 10 L. Koloni terpilih BR7 menghasilkan borrelidin tertinggi. Optimasi media difokuskan pada empat variabel (tepung beras, glukosa, soybean meal, dan ekstrak yeast) menggunakan response surface methodology–Box–Behnken design (RSM-BBD). Sebanyak 29 eksperimen dilakukan selama 7 hari fermentasi pada suhu 28 °C dan 220 rpm, konsentrasi borrelidin ditentukan menggunakan HPLC. Analisis statistik menunjukkan biosintesis borrelidin secara signifikan dipengaruhi oleh efek kuadratik dan interaksi sumber karbon–nitrogen. Komposisi media optimal (tepung beras 30,6 g/L; glukosa 26,3 g/L; soybean meal 20,0 g/L; dan ekstrak yeast 2,8 g/L) meningkatkan titer borrelidin hingga empat kali lipat (83 mg/L), sesuai prediksi model. Peningkatan skala fermentasi pada bioreaktor 10 L menghasilkan titer 120 mg/L, ini menegaskan efektivitas RSM-BBD dalam optimasi media dan membuka peluang produksi borrelidin pada skala industri untuk pengembangan turunan farmasetik melalui modifikasi struktur.
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Borrelidin is a macrolide compound with diverse bioactivities, including potent antimalarial activity (IC₅₀ 0.9 ng/L), however it also shows high cytotoxicity against MRC-5 cells (IC₅₀ 410 nM). Despite its toxicity, borrelidin remains a promising candidate for antimalarial drug development through chemical structure modification aimed at reducing cytotoxicity. Large-scale availability of borrelidin is essential for drug development, yet fermentation yield from Streptomyces rochei remains low. This study aimed to enhance borrelidin productivity by an endophytic S. rochei strain isolated from the medicinal plant Lempuyang through colony selection, media optimization, and scale-up fermentation in a 10 L bioreactor. The selected colony, BR7, produced the highest borrelidin yield. Media optimization focused on four variables (rice flour, glucose, soybean meal, and yeast extract) using response surface methodology–Box Behnken design (RSM-BBD). A total of 29 experiments were conducted over 7 days of fermentation at 30 °C and 220 rpm, with borrelidin concentration determined by HPLC. Statistical analysis revealed that borrelidin biosynthesis was mainly influenced by quadratic effects and carbonnitrogen source interactions. The optimal media formulation (rice flour 30.6 g/L; glucose 26.3 g/L; soybean meal 20.0 g/L; ekstrak yeast 2.8 g/L) increased yield fourfold (83 mg/L), consistent with model predictions. Scale-up fermentation in a 10 L bioreactor further enhanced yield to 120 mg/L. These findings confirm the effectiveness of RSM-BBD in media optimization and underscore the potential for industrial-scale borrelidin production, opening opportunities for pharmaceutical derivatives through structural modification.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | Kata Kunci: borrelidin, seleksi koloni, fermentasi, media, Response surface methodology-BBD Keywords: borrelidin, colony selection, fermentation, media, RSM-BBD |
| Subjects: | Q Science > QD Chemistry > QD251.2 Chemistry, Organic. Biochemistry |
| Divisions: | Faculty of Natural Science > Chemistry > 47001-(S3) PhD Thesis |
| Depositing User: | Diana Dewi |
| Date Deposited: | 05 Aug 2026 07:33 |
| Last Modified: | 05 Aug 2026 07:33 |
| URI: | http://repository.its.ac.id/id/eprint/144068 |
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