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Alkafoids are an important type of natural products,most of which are produced by plants and about one-third are produced by microorganisms.Alkaloids show vast chemo-diversity and exhibit diverse biological activity,playing important roles in drug discivery and development.We chose a group alkaloids including strptonigrinoids,maremycins,and FR-900452 that contain a p-methyltryptophan moiety produced by actinomycetes as our tartget molecules.Streptonigrinoids show strong antimicrobial,antiviral,and antitumor activity; maremycins are active against leukemia cell line; PR-900452 acts as a platelet-activating factor antagonist.We cloned and sequenced their biosynthetic gene clusters and proposed their corresponding biosynthetic pathways.The enzymatic mechanism of enantiospecific formation of(25,35)-and(2S,3R)-β-methyl tryptophan has been demonstrated by using isotope-labeled substrate and protein mutageneses.The identification of gene clusters and biosyntheic pathways set a stage to further investigate the enzymatic mechanism of the biosynthesis of these microbial alkaloids and to create their analogues with structural modification and potent activity as potential therapeutic agents by pathway engineering.