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Thielavins as Glucose-6-phosphatase (G6Pase) Inhibitors: Producing Strain, Fermentation, Isolation, Structural Elucidation and Biological Activities.

2002; Springer Nature; Volume: 55; Issue: 11 Linguagem: Inglês

10.7164/antibiotics.55.941

1881-1469

Shinichi Sakemi, Hideo Hirai, Toshio Ichiba, TAISUKE INAGAKI, Yoshinao Kato, Nakao Kojima, Hiroyuki Nishida, Janice C. Parker, Toshiyuki Saito, Hiroko Tonai‐Kachi, Maria A. VanVolkenburg, Nobuji Yoshikawa, Yasuhiro Kojima,

Enzyme Catalysis and Immobilization

High-throughput screening of microbial extracts using rat hepatic microsomal glucose-6-phosphatase (G6Pase) led us to find thielavin B as a G6Pase inhibitor with inhibition of glucose output from glucagon-stimulated hepatocytes. Further searching for more potent analogs identified 11 new thielavins F-P in addition to the known thielavins A and B from a fungus Chaetomium carinthiacum ATCC 46463. Thielavin G showed the strongest activity as a G6Pase inhibitor (IC50=0.33μM), while the IC50 of thielavin B was 5.5μM. According to the structureactivity relationship, including authentic thielavins C, D and 3 partial hydrolysates from thielavins A and B, 3 benzoic acid-units and carboxylic acid functions are essential for G6Pase inhibition.