Study On The Biosynthesis Pathway Of Streptovaricin C

Streptovaricin C is a type of naphthalenic ansamycin with the basic carbon skeleton composed of naphthalene rings,fatty long chains and amide bonds which generated during the extension process by polyketide synthase,and then forms the final product through a series of post-modifications.Streptovaricins have a wide range of biological activities,such as anti-Mycobacterium tuberculosis and anti-methicillin-resistant Staphylococcus aureus,and anti-virus activity,while its biosynthetic machanisms has not been extensively studied yet.Thus,this study aims to reveal the biosynthetic process of naphthalene acetylation and methylene dioxygen bridge in Streptovaricin C produced by Streptomyces spectabilis ATCC M2017417,which is isolated from the soil of the campus of Wuhan University.With the bioinformatics analysis and a series techniques of molecular genetics,in-vitro enzymology and chemistry,it is successfully proved that in the biosynthesis of Streptovaricin C,the methyltransferase Stv M1 is responsible for the methylation of the C-6 hydroxyl,the acyltransferase Stv A2 is responsible for the acetylation of the naphthalene ring and the fatty chain hydroxyl,and the cytochrome P450 protein Stv P2 is responsible for the formation of methylene dioxygen bridge between C-6 and C-11.Moreover,the biosynthetic order is also determined that the methylation occurs first,followed by naphthalene ring acetylation,and finally a methylene dioxygen bridge is formed.In conclusion,this study not only enriched the understanding about the biosynthesis of Streptovaricins antibiotics,but also contributed to the rational modification of Streptovaricin and ansamycin antibiotics.