Biosynthesis of the cyclooligomer depsipeptide bassianolide, an insecticidal virulence factor of Beauveria bassiana.
Beauveria bassiana is a facultative entomopathogen with an extremely broad host range that is used as a commercial biopesticide for the control of insects of agricultural, veterinary and medical significance. B. bassiana produces bassianolide, a cyclooligomer depsipeptide secondary metabolite. We have cloned the bbBsls gene of B. bassiana encoding a nonribosomal peptide synthetase (NRPS). Targeted inactivation of the B. bassiana genomic copy of bbBsls abolished bassianolide production, but did not affect the biosynthesis of beauvericin, another cyclodepsipeptide produced by the strain. Comparative sequence analysis of the BbBSLS bassianolide synthetase revealed enzymatic domains for the iterative synthesis of an enzyme-bound dipeptidol monomer intermediate from d-2-hydroxyisovalerate and l-leucine. Further BbBSLS domains are predicted to catalyze the formation of the cyclic tetrameric ester bassianolide by recursive condensations of this monomer. Comparative infection assays against three selected insect hosts established bassianolide as a highly significant virulence factor of B. bassiana.
Xu
Yuquan
Y
SW Center for Natural Products Research and Commercialization, The University of Arizona, Tucson, 85706-6800, USA.
Orozco
Rousel
R
Kithsiri Wijeratne
E M
EM
Espinosa-Artiles
Patricia
P
Leslie Gunatilaka
A A
AA
Patricia Stock
S
S
Molnár
István
I
D000595:Amino Acid Sequence; D000818:Animals; D052982:Beauveria / Q000378:metabolism*; D020134:Catalytic Domain; D003001:Cloning, Molecular; D047630:Depsipeptides / Q000096:biosynthesis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D018390:Gene Targeting; D007313:Insecta / Q000187:drug effects; D007306:Insecticides / Q000378:metabolism* / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D017421:Sequence Analysis; D016019:Survival Analysis; D014631:Valerates / Q000378:metabolism; D037521:Virulence Factors / Q000096:biosynthesis*
D047630:Depsipeptides; D005656:Fungal Proteins; D007306:Insecticides; D010456:Peptides, Cyclic; D014631:Valerates; D037521:Virulence Factors; C035864:2-hydroxyisovaleric acid; C004456:beauvericin; C035050:bassianolide; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase; D007930:Leucine