Synergistic Actions of Tailoring Enzymes in Pradimicin Biosynthesis

Overview

Journal Chembiochem

Specialty Biochemistry

Date 2014 Aug 27

PMID 25155298

Citations 2

Authors

Kandy Napan

Shuwei Zhang

Whitney Morgan

Thomas Anderson

Jon Y Takemoto

Jixun Zhan

Affiliations

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Abstract

Three key tailoring enzymes in pradimicin biosynthesis: PdmJ, PdmW, and PdmN, were investigated. PdmW was characterized as the C-6 hydroxylase by structural characterization of the corresponding product, 6-hydroxy-G-2A. The efficiencies of the C-5 and C-6 hydroxylations, catalyzed respectively by PdmJ and PdmW, were low when they were expressed individually with the early biosynthetic enzymes that form G-2A. When these two cytochrome P450 enzymes were co-expressed, a dihydroxylated product, 5,6-dihydroxy-G-2A, was efficiently produced, indicating that these two enzymes work synergistically in pradimicin biosynthesis. Heterologously expressed PdmN in Streptomyces coelicolor CH999 converted G-2A to JX137a by ligating a unit of D-alanine to the carboxyl group. PdmN has relaxed substrate specificity toward both amino acid donors and acceptors. Through combinatorial biosynthesis, a series of new pradimicin analogues were produced.

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