Alkaloid natural products generally have complex and diverse chemical structures and exhibit a wide range of biological activities, and therefore are of great interest to biologists, chemists, and pharmacists. Apart from plants, microorganisms have been identified as the most important source of natural alkaloids. Microorganisms, especially actinomycetes, produce many secondary metabolites including alkaloids. Studies on the biosynthesis of skeletons and pharmacophores of alkaloids produced by actinomycetes not only enrich our understanding of the biosynthetic mechanism of natural products, but also provide important genetic elements in order to generate these compounds or the derivatives by designed and man-made synthetic pathways in heterologous host using synthetic biology. This review provides a summary of recent research advances in elucidating the biosynthesis of alkaloids from actinomycetes. The detailed biochemical mechanisms have been summarized in modular biosynthetic machineries and non-modular enzymatic systems, respectively.
Contents
1 Introduction
2 Modular biosynthesis of alkaloids
2.1 Diketopiperazine alkaloids
2.2 Pyrrolobenzodiazepines
2.3 Tetrahydroisoquinolines
2.4 Maremycins family
3 Non-modular biosynthesis of alkaloids
3.1 Streptonigrinoids
3.2 Spirocycloproprane family
3.3 Indolocarbazole alkaloids
3.4 Aminobenzoquinone-aziridine alkaloids
4 Conclusion and outlook