What is a HMA?

Hydroxy-mandelic acid (HMA) is widely used in the production of aromatic drugs and spices^[1]. It can be used to prepare selectiveβ1-receptor antagonist atenolol and synthetic precursors of several non-ribosomal antibiotics^[2].Moreover, p-hydroxymandelic acid shows promising applications in targeted drug delivery systems. But its market price is as high as $14,000 per kilogram, and its chemical synthesis methods have adverse environmental effects. Its biological methods have received a lot of attention recently.

The synthesis of HMA

As industries are evolving toward sustainable and environmental-friendly, microbial synthesis of these compounds attracted increasing attention^[3]. Microbial metabolism has been harnessed to provide us access to natural products that are needed for the survival and reproduction of the host organisms, leading to the challenge in achieving high yields of desired products. In recent years, the iterative “design-build-test-learn” cycle of the synthetic biology has enabled rapid design and generation of highly diverse libraries. However, screening for desirable variants remains a critical bottleneck, underlining the need for high-throughput approaches to easily identify candidate phenotypes^[4].

In recent years, the development of directed evolution has broadened the design scope of protein engineering, which can modify proteins without knowing the structural information and mechanism of action of target proteins. We boldly attempted directed evolution of strains, reasonably designed and altered metabolic pathways to obtain our target strains.

With the popularity of AlphaFold2 this year, we wondered if we could use protein structure prediction to better understand how individual amino acid site changes would affect the PobR protein pocket. So we tried to use bioinformatics methods to do molecular docking.