Abstract

In this work, we investigated the effect of pH on Streptomyces M37 growth and its acarbose biosynthesis ability. We observed that low pH was beneficial for cell growth, whereas high pH favored acarbose synthesis. Moreover, addition of glucose and maltose to the fermentation medium after 72 h of cultivation promoted acarbose production. Based on these results, a two-stage fermentation strategy was developed to improve acarbose production. Accordingly, pH was kept at 7.0 during the first 72 h and switched to 8.0 after that. At the same time, glucose and maltose were fed to increase acarbose accumulation. With this strategy, we achieved an acarbose titer of 6210 mg/L, representing an 85.7% increase over traditional batch fermentation without pH control. Finally, we determined that the increased acarbose production was related to the high activity of glutamate dehydrogenase and glucose 6-phosphate dehydrogenase.

Highlights

  • Acarbose is a competitive α-glucosidase inhibitor [1] widely used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) [2,3]

  • We investigated the effect of feeding glucose and maltose to promote acarbose production

  • Our results indicated that pH played an important role in cell growth and acarbose biosynthesis during the fermentation process

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Summary

Introduction

Acarbose (acarviosyl-1,4-maltose) is a competitive α-glucosidase inhibitor [1] widely used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) [2,3]. Acarbose is a complex oligosaccharide known to reduce and slow down the intestinal absorption of glucose. As a result, it lowers the postprandial increase in blood glucose levels in NIDDM patients. Its medical effect is based on a decreased release of glucose from starch- and sucrose-containing foods in the human intestine, which leads to reduced levels of blood glucose and serum insulin [4]. Acarbose was identified in strains of the genera Actinoplanes and Streptomyces [5,6]. It was reported to belong to a mixed-growth-associated type of secondary metabolites; its biosynthesis being independent of cell growth [7]

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