Improved Lovastatin Production via Targeted Medium Supplementation in Aspergillus terreus.

IF 2.7 4区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Maryam Javanpour, Ramtin Vamenani, Ethan Brister
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Abstract

Lovastatin is a clinically crucial cholesterol-lowering agent produced by Aspergillus terreus; however, its commercial biosynthesis remains limited due to suboptimal fermentation conditions. This study addresses the challenge of evaluating how the supplementation of l-cysteine (l-Cys), linoleic acid (LA), and riboflavin (vitamin B2) individually, in dual combinations, and, as a triple formulation, affects both fungal biomass and lovastatin yield. Among individual supplements, LA had the most pronounced effect, increasing lovastatin production to 1892.43 mg/L, whereas l-Cys and B2 yielded 1600.66 and 1176.82 mg/L, respectively. Dual combinations, such as l-Cys + LA and LA + B2, produced higher titers (2300 and 2282.96 mg/L, respectively), leading to significant increases in yield per gram of biomass. The highest productivity was achieved with triple supplementation (115 mg/L l-Cys + 90 mg/L LA + 0.66 mg/L B2), resulting in 2373.99 mg/L lovastatin, a biomass of 8.03 g/L, and a yield of 295.65 mg/g biomass. Biomass measurements across all treatments indicated that although fungal growth was moderately enhanced, the increase in lovastatin production was disproportionately greater. This suggests that the supplements primarily stimulate metabolic flux toward polyketide synthesis. These findings provide a foundation for media optimization strategies to enhance industrial-scale lovastatin production through precise nutrient control.

通过在地曲霉中添加靶向培养基提高洛伐他汀产量。
洛伐他汀是临床上重要的降胆固醇药物,由地曲霉产生;然而,由于发酵条件欠佳,其商业化生物合成仍然受到限制。本研究解决了评估l-半胱氨酸(l-Cys)、亚油酸(LA)和核黄素(维生素B2)单独、双重组合和三重组合如何影响真菌生物量和洛伐他汀产量的挑战。在单个补充物中,LA的效果最为显著,可使洛伐他汀产量增加至1892.43 mg/L,而L - cys和B2的产量分别为1600.66和1176.82 mg/L。L - cys + LA和LA + B2的双重组合可产生更高的滴度(分别为2300和2282.96 mg/L),从而显著提高每克生物量的产量。结果表明,三组分(115 mg/L L - cys + 90 mg/L LA + 0.66 mg/L B2)的洛伐他汀产量为2373.99 mg/L,生物量为8.03 g/L,产率为295.65 mg/g。所有处理的生物量测量表明,尽管真菌生长适度增强,但洛伐他汀产量的增加不成比例地更大。这表明,补充剂主要刺激代谢通量向聚酮合成。这些发现为通过精确的营养控制提高洛伐他汀工业规模生产的培养基优化策略提供了基础。
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来源期刊
Biotechnology and applied biochemistry
Biotechnology and applied biochemistry 工程技术-生化与分子生物学
CiteScore
6.00
自引率
7.10%
发文量
117
审稿时长
3 months
期刊介绍: Published since 1979, Biotechnology and Applied Biochemistry is dedicated to the rapid publication of high quality, significant research at the interface between life sciences and their technological exploitation. The Editors will consider papers for publication based on their novelty and impact as well as their contribution to the advancement of medical biotechnology and industrial biotechnology, covering cutting-edge research in synthetic biology, systems biology, metabolic engineering, bioengineering, biomaterials, biosensing, and nano-biotechnology.
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