Tailoring enzymes involved in the biosynthesis of angucyclines contain latent context-dependent catalytic activities.
Comparison of homologous angucycline modification enzymes from five closely related Streptomyces pathways (pga, cab, jad, urd, lan) allowed us to deduce the biosynthetic steps responsible for the three alternative outcomes: gaudimycin C, dehydrorabelomycin, and 11-deoxylandomycinone. The C-12b-hydroxylated urdamycin and gaudimycin metabolites appear to be the ancestral representatives from which landomycins and jadomysins have evolved as a result of functional divergence of the ketoreductase LanV and hydroxylase JadH, respectively. Specifically, LanV has acquired affinity for an earlier biosynthetic intermediate resulting in a switch in biosynthetic order and lack of hydroxyls at C-4a and C-12b, whereas in JadH, C-4a/C-12b dehydration has evolved into an independent secondary function replacing C-12b hydroxylation. Importantly, the study reveals that many of the modification enzymes carry several alternative, hidden, or ancestral catalytic functions, which are strictly dependent on the biosynthetic context.
Department of Biochemistry and Food Chemistry, University of Turku, 20014 Turku, Finland.
Pekka
P
Patrikainen
Pauli
P
Kallio
Keqiang
K
Fan
Karel D
KD
Klika
Khaled A
KA
Shaaban
Pekka
P
Mäntsälä
Jürgen
J
Rohr
Keqian
K
Yang
Jarmo
J
Niemi
Mikko
M
Metsä-Ketelä
D000617:Aminoglycosides / Q000737:chemistry / Q000378:metabolism; D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D048170:Streptomyces lividans / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism
D000617:Aminoglycosides; D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; D009844:Oligosaccharides; C528940:gaudimycin C; C490011:landomycinone; C052535:urdamycin C; D006899:Mixed Function Oxygenases; D016695:Glycosyltransferases; C514966:LanV enzyme, Streptomyces