Identification and Characterization of Enzymes Catalyzing Early Steps in Miharamycin and Amipurimycin Biosynthesis

Abstract

The biochemical elucidation of the early biosynthetic pathways of miharamycins and amipurimycin revealed the roles of several enzymes, which include GMP hydrolase, represented by MihD/ApmD, and hypothetical proteins, MihI/ApmI, unexpectedly exhibiting the dual function of the guanylglucuronic acid assembly and GMP cleavage. In addition, MihE, a carbonyl reductase that functions on the C2 branch of high-carbon sugars, and MihF, a rare guanine O-methyltransferase, were also functionally verified.

Purine nucleoside antibiotics: recent synthetic advances harnessing chemistry and biology

“…7 ). 62 MihI is responsible first for the anomeric hydrolysis of GMP (46), followed by use of the released guanine for the formation of a new C–N bond via reaction with the sugar nucleotide donor, UDP-GlcA. This reaction is particularly interesting as it incorporates a pyranose in place of ribose.…”

Post‐Modification of Amino Acids and Peptides for the Rapid Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

“…C ‐glycoamino acids and glycoproteins have been found as important skeletons in natural products, such as Amipurimycin ( 1 ), [23–27] Nikkomycin Z ( 2 ), [28–32] and Lincomycin ( 3 ) [33–37] with antibiotic activities, as well as a decamer glycopeptide hormone Cam‐HrTH‐I ( 4 ) (Figure 1). [38–41] Despite of their less occurrence of C ‐glycoamino acids and glycoproteins in nature compared with O‐ / N ‐glycoamino acids and glycoproteins, they showed improved biological activity compared to their naturally occurring analogues [15,42–44] .…”