The present invention provides polypeptides that participate in the biosynthesis of the pladienolide macrolide compounds, DNA that encodes these polypeptides and variants of this DNA, transformants that maintain all or a portion of this DNA or variant thereof, and a method of producing the pladienolide macrolide compounds using these transformants. More particularly, it provides an isolated pure DNA that contains at least one region encoding a polypeptide that participates in pladienolide biosynthesis; polypeptide encoded by this DNA; a self-replicating or integrated-replicating recombinant plasmid carrying this DNA; a transformant maintaining this DNA; and a method of producing a pladienolide, characterized by culturing this transformant on culture medium and collecting pladienolide from this culture medium.