Microbial production of meroterpenes and alkaloids via synthetic biology

Abstract

Plants produce a large diversity of bioactive molecules of low molecular weight, while the utilization of those chemicals has been still limited due to the low content and complex mixture in plant tissues. To overcome these limitations, microbial production of phytochemicals has been developed in recent years using synthetic biology-based approaches. Meroterpenes form a composite-type metabolite group composed of phenolics and terpenoids, and thus far approximately 1,000 chemical structures have been elucidated. A variety of bioactivities such as anti-inflammatory and anti-obesity have been reported with prenyl side chains often crucial to functions of meroterpenes, and moreover, anti-SARS-CoV-2 activities are also expected. The prenyl chains are transferred to phenolic core structures by the UbiA-type prenyltransferase (PT) family. This review summarizes recent advances in the key enzyme family and meroterpene production in microorganisms. In synthetic biology, breakthroughs have been consecutively reported on microbial production of clinically used alkaloids, such as opioids, tropane alkaloids, and monoterpene indole alkaloids. These molecules are produced via highly complicated biosynthetic pathways spanning multiple organelles and cell types in plants. We also explain cutting-edge techniques leading to the functional reconstruction of biosynthetic pathways of these metabolites.