8H3T

The crystal structure of AlpH

Summary for 8H3T

• Entry DOI: 10.2210/pdb8h3t/pdb
• Descriptor: AlpH, GLYCEROL (3 entities in total)
• Functional Keywords: alph, lyase
• Biological source: Streptomyces galtieri
• Total number of polymer chains: 2
• Total formula weight: 77366.68

Authors

Zhao, Y.,Li, M.,Jiang, M.,Pan, L.F. (deposition date: 2022-10-09, release date: 2023-09-13, Last modification date: 2024-02-14)

Primary citation

Zhao, Y.,Liu, X.,Xiao, Z.,Zhou, J.,Song, X.,Wang, X.,Hu, L.,Wang, Y.,Sun, P.,Wang, W.,He, X.,Lin, S.,Deng, Z.,Pan, L.,Jiang, M.
O-methyltransferase-like enzyme catalyzed diazo installation in polyketide biosynthesis.
Nat Commun, 14:5372-5372, 2023

PubMed Abstract: Diazo compounds are rare natural products possessing various biological activities. Kinamycin and lomaiviticin, two diazo natural products featured by the diazobenzofluorene core, exhibit exceptional potency as chemotherapeutic agents. Despite the extensive studies on their biosynthetic gene clusters and the assembly of their polyketide scaffolds, the formation of the characteristic diazo group remains elusive. L-Glutamylhydrazine was recently shown to be the hydrazine donor in kinamycin biosynthesis, however, the mechanism for the installation of the hydrazine group onto the kinamycin scaffold is still unclear. Here we describe an O-methyltransferase-like protein, AlpH, which is responsible for the hydrazine incorporation in kinamycin biosynthesis. AlpH catalyses a unique SAM-independent coupling of L-glutamylhydrazine and polyketide intermediate via a rare Mannich reaction in polyketide biosynthesis. Our discovery expands the catalytic diversity of O-methyltransferase-like enzymes and lays a strong foundation for the discovery and development of novel diazo natural products through genome mining and synthetic biology.

PubMed: 37666836
DOI: 10.1038/s41467-023-41062-7

Experimental method

X-RAY DIFFRACTION (1.866 Å)