Research reveals how key diabetes drug is made in nature

Actinoplanes. SE50/110. A cluster of Acarbose biosynthetic genes from Actinoplanes. SE50/110. b Proposed Acarbose biosynthetic routes. The thick purple (shaded with blue) arrows indicate steps that have already been biochemically characterized before this study. The blue and red arrows indicate previously suggested pathways. The thick black arrows, highlighted in yellow, indicate the path elucidated by this study. SH7P, sedoheptulose 7-phosphate; EEV, 2-epi-5-epi-valiolone; EEV7P, 2-epi-5-epi-valiolone 7-phosphate; EV7P, 5-epi-valiolone 7-phosphate; V1P, valienol 1-phosphate; V7P, valienol 7-phosphate; 1-epi-V7P, 1-epi-valienol 7-phosphate; V1,7PP, valienol 1,7-diphosphate; 1-epi-V1,7PP, 1-epi-valienol 1,7-diphosphate; NDP-V, nucleoside diphosphate-valienol; NDP-V7P, nucleoside diphosphate-valienol 7-phosphate; NDP-1-epi-V7P, nucleoside diphosphate-1-epi-valienol 7-phosphate; dTDP-4a6dGlc, dTDP-4-amino-4,6-dideoxyglucose; 4-aminoDGG, O-4-amino-(4,6-dideoxy-α-D-glucopyranosyl)-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-glucopyranose. Credit: Nature Communications (2022). DOI: 10.1038/s41467-022-31232-4

Oregon State University researchers have revealed how a vital type 2 diabetes drug is made naturally, opening up the possibility of biotechnology-based manufacturing improvements.

The findings are particularly important because global demand for the drug, acarbose, is rising along with incidence of type 2 diabetes—according to the International Diabetes Federation, the disease affects nearly 500 million adults worldwide.

Bayer developed the drug, which has been on the marketplace under the brand Precose ever since 1996. Acarbose comes from soil bacteria but until now the biosynthetic pathway underlying its production—the sequence of steps taken by enzymes to catalyze the chemical reactions responsible for making it—was not known.

The results of the study, conducted by Taifo Mahamud of OSU College of Pharmacy were published in Nature Communications.

Type 2 diabetes, which is often associated with obesity and low levels of physical activity, is a serious metabolic condition that affects approximately one in 10 Americans. It was previously known as adult-onset diabetes. It is a chronic condition that affects the body’s ability to metabolize glucose, a vital source of energy.

For some patients, that means their body does not properly respond to insulin—it resists the effects of insulin, the hormone produced by the pancreas that opens the door for sugar to enter cells. Patients with advanced disease don’t produce enough insulin to maintain normal glucose levels.

In either case, sugar builds-up in the bloodstream, which can lead to serious health problems, including life-threatening or disabling effects.

Acarbose normalizes blood glucose levels by inhibiting alpha-glucosidase enzymes—it helps keep blood sugar from rising too quickly after someone eats by blocking the breakdown of starchy foods like bread, potatoes and pasta and slowing down the intestinal absorption of some sugars.

Acarbose comes from Actinoplanes bacteria, as well as several other strains soil bacteria. It was the first alphaglucosidase inhibitor approved for use in Europe or the United States.

Mahmud stated, “Despite its therapeutic importance, we still don’t know how acarbose was made in nature.” “Our research not only sheds light on how this high-value pharmaceutical is made in nature but also provides a platform for further improvements of industrial acarbose production—for example, by modifying the DNA of the producing bacteria or through other biotechnological approaches. It is therefore important to know the entire biosynthetic process from both a scientific as well as industrial perspective.

What remains unknown, Mahmud added, is why soil bacteria produce acarbose—what purpose does the compound serve for them? Some hypothesize that it plays a role in shuttling sugars between bacteria’s intra- and extracellular spaces or that it protects against the carbohydrate-degrading enzymes of other organisms.

“What the function of the organisms that produce them in their natural environment is an exciting topic for future study,” he stated.

Research reveals why not all obese people develop type 2 diabetes

More information:
Takeshi Tsunoda, et al. Complete biosynthetic pathway to antidiabetic drug Acarbose. Nature Communications (2022). DOI: 10.1038/s41467-022-31232-4

Provided by
Oregon State University

Research shows how a key diabetes drug is made in the natural world (2022, June 21).
Retrieved 22 June 2022
from https://medicalxpress.com/news/2022-06-reveals-key-diabetes-drug-nature.html

This document is subject copyright. Except for fair dealings for private study or research purposes, there is no
Part may not be reproduced without written permission. This content is only for informational purposes.

Source: medical xpress.

Leave a Reply

Your email address will not be published.

Back to top button