Recently, the research team of ZHENG Zhiming in Hefei Institutes of Physical Science constructed a novel VK₂ biosynthetic pathway in Pichia pastoris through the concepts of synthetic biology.

Over the past few years, numerous studies have indicated that the menaquinones (MKs) can play a role in treating mitochondrial pathologies such as Parkinson’s disease and amyotrophic lateral sclerosis, and even exhibiting anticancer activity in several types of cancer cells, including liver cancer, lung cancer, bladder cancer, prostate cancer and ovarian cancer.

However, the synthesis of MKs is complicated and time-cost.

To solve these problems, ZHENG’s team first achieved whole-cell catalytic synthesis of MK-4 in Pichia pastoris.

They realized heterologous expression of aromatic prenyltransferase HsUBIAD1, which has the ability to catalyze the biosynthesis of MK-4 by the isopentenyl receptor VK₃.

On this basis, rDNA-mediated multi-copy expression vector was developed to realize the fusion expression of SaGGPPS and PpIDI, further strengthen the supply of isopentenyl pyrophosphate side chain and promote the biosynthesis of MK-4.

The study lays foundation for the rational design and construction of cell factories to biosynthesize prenylated menadione derivatives, and provides guidance for biosynthesis of high-value chemicals.

The research was supported by the National High-Tech Research and Development Program of China, and the Major Project of Science and Technology in Anhui Province.

Biosynthetic pathway for MK-4 in P. pastoris GS115. (Image by SUN Xiaowen)