Biosynthesis of the l -Pyridylalanine Moiety in Antimycobacterial Pyridomycin via a PKS-NRPS Hybrid System

Organic Letters 2026

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Authors: Haibo Du, Zihua Zhou, Shuang Han, Xiaozheng Wang, Tingting Huang, Shuangjun Lin
DOI: 10.1021/acs.orglett.6c00232
Cited by: 1
References: 29

Abstract

biosynthesis of 3-(3-pyridyl)-l-alanine (3-Pal), a key structural motif of the antimycobacterial cyclodepsipeptide pyridomycin, through a coordinated nonribosomal peptide synthetase-polyketide synthase (NRPS-PKS) hybrid system. Nicotinic acid and 1,3-bisphosphoglycerate (1,3-BPG) are separately activated and loaded onto carrier proteins, forming two tethered intermediates. The type I PKS enzyme Pyr9 catalyzes their condensation, followed by hydrolysis and transamination, ultimately yielding 3-Pal. This work significantly expands the functional versatility of NRPS-PKS biosynthetic machinery.

Fields of Study & Subjects

Microbial Natural Products and Biosynthesis Enzyme Structure and Function Carbohydrate Chemistry and Synthesis

Publication details

Journal / source
Organic Letters
Publisher
American Chemical Society (ACS)
Volume
28
Issue
9
Pages
2971–2976
Publication date
23 February 2026
Language
EN