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Scientists Construct a Novel Menaquinone-4 Biosynthetic Pathway in Pichia pastoris

Recently, the research team of ZHENG Zhiming constructed a novel VK2 biosynthetic pathway in Pichia pastoris through the concepts of synthetic biology. Their study was published in Microbial Cell Factories with the title of “Construction of a novel MK-4 biosynthetic pathway in Pichia pastoris through heterologous expression of HsUBIAD1”.

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 exhibit 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 complicate and time cost.

To solve these problems, ZHENG’s team first achieved whole-cell catalytic synthesis of MK-4 in Pichia pastoris. They achieved 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 constructed 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 the foundation for the rational design and construction of cell factories to biosynthesize prenylated menadione derivatives, and has guiding significance for biosynthesis of high-value chemicals.

The research was supported and 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)