Hydroxybenzoic acids: Microbial metabolism, pathway engineering and products

Hydroxybenzoic acids (HBAs) are plant secondary metabolites exhibiting antioxidant, antiviral, anticancer and antibacterial activities. A high and constantly increasing demand for these compounds underlines the need for novel and efficient production methods, as commonly applied plant extraction and chemical synthesis approaches are susceptible to low yields and are environmentally hazardous. Switching to biotechnology and replacing petroleum-based chemicals has potential to improve eco-efficiency in sustainable bioeconomy. With the increased focus on the production of materials using renewable resources and bio-based feedstocks, microbial fermentation and engineering drives the development and optimization of sustainable bioproduction. This systematic review summarizes current knowledge of microbial HBAs metabolism and biosynthesis. Here, the existing challenges are highlighted and the potential strategies for improved microbial production of HBAs are identified. Key aspects of HBAs metabolism and complexity of the factors related to bacterial strain selection, titer, and bioprocess strategy are examined. The opportunities of HBAs bioproduction using engineered microbial cell factories are discussed in detail and insights for synthesis improvement are presented.