The molecular complexity of terpene biosynthesis in red algae: current state and future perspectives

Covering the period 1998-2024Red algae are the largest group of seaweeds and rich sources of bioactive terpenes with broad and significant biotechnological potential. However, the main obstacle to the economic exploitation of these compounds is the difficulty of obtaining them on an industrial and sustainable scale. Genetic engineering and heterologous biosynthesis are promising tools for overcoming this limitation, but little is known about red algal terpene biosynthetic routes. In general, terpene biosynthesis relies on complex mechanisms that produce a wide array of chemically diverse compounds. In this article, we review the main processes that contribute to such chemical diversity of terpenes, which are divided into four biosynthetic steps: (i) biosynthesis of isoprenoid precursors, (ii) linear condensation of precursors to produce polyisoprenyl diphosphate intermediary molecules, (iii) terpene synthase-catalyzed chemical/structural modifications, and (iv) additional chemical/structural modifications on the basic terpene carbon skeleton. Terpene synthase evolution in algae and topics that have only recently been explored, such as terpene synthase catalytic and substrate promiscuity, have also been analyzed in detail. We present a detailed analysis of terpenoid metabolism in red algae, highlighting the mechanisms that generate their chemical diversity and identifying knowledge gaps. Additionally, we provide perspectives to guide future studies, aiming to advance the heterologous biosynthesis of terpenes from red algae for biotechnological development and application.