We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Formation and Loading of a (2S)‐2‐Ethylmalonamyl Starter Unit in the Assembly Line of Polyketide‐Nonribosomal Peptide Hybrid Sanglifehrin A.
- Authors
Tang, Zhijun; Pang, Bo; Liu, Chang; Guo, Shengjie; Qu, Xudong; Liu, Wen
- Abstract
Sanglifehrin A (SFA) is a spirolactam‐conjugated, 22‐membered macrolide with remarkable immunosuppressive and antiviral activities. This macrolide is a result of a hybrid polyketide synthase (PKS)‐nonribosomal peptide synthetase (NRPS) assembly line that utilizes (2S)‐2‐ethylmalonamyl as a starter unit. Here, we report that the formation and loading of this starter unit in the SFA assembly line involve two unusual enzymatic reactions that occur on a discrete acyl carrier protein (ACP), SfaO. An amide synthetase, SfaP, catalyzes the amidation of (2S)‐2‐ethylmalonyl in a SfaO‐dependent manner. Then, a β‐ketoacyl‐ACP synthase III‐like protein, SfaN, transfers resultant (2S)‐2‐ethylmalonamyl from SfaO onto the loading ACP domain of the hybrid PKS‐NRPS assembly line to prime SFA biosynthesis. Both SfaP and SfaN display promiscuous activities. This study furthers the appreciation of assembly line chemistry, as a new paradigm for unusual building block formation and incorporation is provided.
- Subjects
ASSEMBLY line methods; PEPTIDES; ACYL carrier protein
- Publication
Angewandte Chemie, 2023, Vol 135, Issue 23, p1
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.202217090