Identification and fermentation optimization of a newly isolated strain Bacillus velezensis AmoreLumina for high-yield moranoline production

Abstract

Moranoline (1-Deoxynojirimycin), a rare iminosugar with α-glucosidase inhibitory activity, holds promise as a candidate for diabetes treatment due to its pharmacological properties. However, moranoline is typically found in trace amounts in natural sources, limiting its availability for commercial and medical applications. This study isolated Bacillus velezensis AmoreLumina from traditional Korean fermented soybean food as a novel moranoline producer. Initial optimization of carbon and nitrogen sources using sorbitol and defatted soybean meal (DSM) yielded 1.222 g/L moranoline in batch culture. Fermentation conditions, particularly the oxygen transfer coeff icient (OTC), significantly influenced moranoline biosynthesis. By maintaining similar OTC levels between shake flasks and a fermentor (OTC of 207.6 h-1), we successfully scaled up the process, achieving similar moranoline production levels. Fermentor studies on the effect of OTC on moranoline production revealed that an OTC of 97.0 h 1 achieved the maximum moranoline yield of 2.263 g/L. Sporulation led to a decline in the expression of moranoline biosynthetic genes, thereby reducing moranoline production after 48 h. Fed-batch fermentation effectively delayed sporulation by providing a controlled and continuous supply of substrates. This strategy maintained an active metabolic state in Bacillus velezensis AmoreLumina, extending the production phase and leading to a significantly enhanced moranoline concentration of 3.852 g/L at 96 h. To the best of our knowledge, this study demonstrates the highest production of moranoline from Bacillus species, highlighting the potential of Bacillus velezensis AmoreLumina as an efficient, non-genetically modified (GM) microbial factory for its production.