Beta-carboline alkaloid, preventing glucolipotoxicity of pancreatic beta-cell, isolated from Paenibacillus sp. B03011

Abstract

Abandoned mines are often extremely contaminated by heavy metals and acid, creating a unique bioregion. In the harsh conditions of an abandoned mine, microorganisms are likely to be subjected to substantial levels of competition, which could lead them to develop unique chemical arsenals. In our continuing screening for biologically active secondary metabolites produced by mine microorganisms, two β-carboline alkaloids were isolated from the culture broth of Paenibacillus sp. B03-011. The strain B03-011 was isolated from a heavy metal contaminated soil, which was collected from Poongwon coal mine in Gangwon-do. The strain was cultured in YM liquid medium and the metabolites production was monitored daily by HPLC-MS analysis. The HPLC analysis showed two notable peaks from day 5 culture medium, which were isolated using prep-HPLC, to yield compound 1 (12 mg, 2mg/L) and 2 (6 mg, 1 mg/L). The structures of these compounds were determined as 1-acetyl-β-carboline (1) and 1-acetyl-3-carboxy-β- carboline (2) through comprehensive analyses of NMR and ESI-MS. Compound 1 was reported from various sources such as plant, marine sponge and bacterium, while compound 2 was only reported from plant. This is the first report on the isolation of compound 2 from a microorganism. Type 2 diabetes is characterized by peripheral insulin resistance, pancreatic β-cell dysfunction, and decreased β-cell mass. Glucolipotoxicity is known to play an important role in pancreatic β- cell apoptosis in type 2 diabetes. It is assumed that inhibition of glocolipotoxicity may prevent the progression of diabetes. Compound 1 showed the bioactivity to prevent glucolipotoxicity of pancreatic β-cell. This is first report about the inhibition of glucolipotoxicity by β-carboline compounds.