Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis.
Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins.
Institute for Organic Chemistry, Leibniz University of Hannover, Schneiderberg 1B, 30167, Germany. katherine.williams@oci.uni-hannover.de.
Katherine
K
Williams
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
Agnieszka J
AJ
Szwalbe
Syngenta, Jealott's Hill, Bracknell, Berkshire, RG42 6EY, UK.
Nicholas P
NP
Mulholland
Syngenta, Jealott's Hill, Bracknell, Berkshire, RG42 6EY, UK.
Jason L
JL
Vincent
School of Biological Sciences, Bristol Life Sciences Building, University of Bristol, 24 Tyndall Ave, Bristol, BS8 1TH, UK.
Andrew M
AM
Bailey
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
Christine L
CL
Willis
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
Thomas J
TJ
Simpson
Institute for Organic Chemistry, Leibniz University of Hannover, Schneiderberg 1B, 30167, Germany. russell.cox@oci.uni-hannover.de.|School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. russell.cox@oci.uni-hannover.de.
Russell J
0000-0002-1844-0157
RJ
Cox
D001236:Aspergillus oryzae / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D005658:Fungi / Q000378:metabolism*; D005663:Furans / Q000737:chemistry / Q000378:metabolism; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism; D008299:Maleic Anhydrides / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D005810:Multigene Family; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism
D005663:Furans; D008299:Maleic Anhydrides; C010875:byssochlamic acid; D048630:Polyketide Synthases; D006867:Hydrolases
biosynthesis; cyclization; enzymes; maleidride; polyketides