Characterization of a 3-hydroxyanthranilic acid 6-hydroxylase involved in paulomycin biosynthesis

  • Biochem Biophys Res Commun. 2021 Mar 5:543:8-14. doi: 10.1016/j.bbrc.2021.01.042.
Yong Ding  1 ,  Min Wang  1 ,  Jine Li  2 ,  Pengwei Li  1 ,  Zhenyan Guo  1 ,  Yihua Chen  3
Affiliations
  • 1. State Key Laboratory of Microbial Resources & CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2. State Key Laboratory of Microbial Resources & CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 3. State Key Laboratory of Microbial Resources & CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: [email protected].
PMID: 33493986 DOI: 10.1016/j.bbrc.2021.01.042
Abstract

Paulomycins (PAUs) refer to a group of glycosylated Antibiotics with attractive Antibacterial activities against Gram-positive bacteria. They contain a special ring A moiety that is prone to dehydrate between C-4 and C-5 to a quinone-type form at acidic condition, which will reduce the Antibacterial activities of PAUs significantly. Elucidation of the biosynthetic mechanism of the ring A moiety may facilitate its structure modifications by combinatorial biosynthesis to generate PAU analogues with enhanced bioactivity or stability. Previous studies showed that the ring A moiety is derived from chorismate, which is converted to 3-hydroxyanthranilic acid (3-HAA) by a 2-amino-2-deoxyisochorismate (ADIC) synthase, a 2,3-dihydro-3-hydroxyanthranilic acid (DHHA) synthase, and a DHHA dehydrogenase. Unfortunately, little is known about the conversion process from 3-HAA to the highly decorated ring A moiety of PAUs. In this work, we characterized Pau17 as an unprecedented 3-HAA 6-hydroxylase responsible for the conversion of 3-HAA to 3,6-DHAA by in vivo and in vitro studies, pushing one step forward toward elucidating the biosynthetic mechanism of the ring A moiety of PAUs.

Keywords
3-Hydroxyanthranilic acid 6-hydroxylase; Biosynthesis; Paulomycin; Quinone-like ring A.
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