Synthetic Biology Yields New Steroid Antibiotics

A research group in Japan has taken a synthetic biology approach to the development of steroid antibiotics.

AsianScientist (Jun. 28, 2018) – Researchers at the University of Tokyo, Japan, have developed a method to produce steroid antibiotics that do not cause cross-resistance to other antibiotics. Their findings, published in Nature Communications, demonstrate how synthetic biology could help prevent the rise of antimicrobial resistance.

Natural products have proven to be a valuable source of new drugs. In particular, a group of steroid antibiotic compounds derived from fungi have shown promising antimicrobial activity. However, little is known about the biosynthetic pathways involved in the production of fungal steroid antibiotics such as helvolic acid, hampering efforts to produce these useful compounds at a large scale.

In this study, the research group led by Dr. Hu Dan and Professor Ikuro Abe at the Graduate School of Pharmaceutical Sciences of the University of Tokyo, Japan, identified the biosynthetic enzymes involved in the production of helvolic acids. Using this information, they constructed a helvolic acid-producing system in Aspergillus oryzae, a type of mold commonly known as koji, which is used for fermentation in food production.

The researchers isolated novel helvolic acid analogs by separating biosynthetic intermediates from the system. Remarkably, some of the analogs exhibited stronger antimicrobial activity than helvolic acid. The researchers said that their experimental approach and results may be useful in drug discovery and development.

“In this study, we developed a production system for steroid antibiotics,” said Abe. “Our results could pave the way for the development of a synthetic biology method that can lead to the creation of novel molecular scaffolds for efficient and easy antibiotic drug synthesis.”



The article can be found at: Lv et al. (2017) Biosynthesis of Helvolic Acid and Identification of an Unusual C-4-demethylation Process Distinct From Sterol Biosynthesis.

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Source: University of Tokyo; Photo: Shutterstock.
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