Insights into pyrroindomycin biosynthesis reveal a uniform paradigm for tetramate/tetronate formation.
The natural products pyrroindomycins (PYRs), active against various drug-resistant pathogens, possess a characteristic, cyclohexene ring spiro-linked tetramate moiety. In this study, investigation into PYR biosynthesis revealed two new proteins, both of which, phylogenetically distinct from but functionally substitutable to each other in vivo, individually catalyze a Dieckmann cyclization in vitro for converting an N-acetoacetyl-l-alanyl thioester into a tetramate. Their counterparts are commonly present in the biosynthetic pathways of spiro and polyether tetronates, supporting a uniform paradigm for tetronate/tetramate formation, which features an enzymatic way to generate the C-X (X = O or N) bond first and the C-C bond next in building of the 5-membered heterocycle.
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Qiongqiong
Q
Wu
Zhuhua
Z
Wu
Xudong
X
Qu
Wen
W
Liu
D055162:Biocatalysis; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D003500:Cyclization; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000378:metabolism*; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism
D001688:Biological Products; D047029:Lactams, Macrocyclic; D018942:Macrolides; C091121:pyrroindomycin A; C091122:pyrroindomycin B; D048630:Polyketide Synthases; D010453:Peptide Synthases