Biosynthesis of the cyclooligomer depsipeptide beauvericin, a virulence factor of the entomopathogenic fungus Beauveria bassiana.
Beauvericin, a cyclohexadepsipeptide ionophore from the entomopathogen Beauveria bassiana, shows antibiotic, antifungal, insecticidal, and cancer cell antiproliferative and antihaptotactic (cell motility inhibitory) activity in vitro. The bbBeas gene encoding the BbBEAS nonribosomal peptide synthetase was isolated from B. bassiana and confirmed to be responsible for beauvericin biosynthesis by targeted disruption. BbBEAS utilizes D-2-hydroxyisovalerate (D-Hiv) and L-phenylalanine (Phe) for the iterative synthesis of a predicted N-methyl-dipeptidol intermediate, and forms the cyclic trimeric ester beauvericin from this intermediate in an unusual recursive process. Heterologous expression of the bbBeas gene in Escherichia coli to produce the 3189 amino acid, 351.9 kDa BbBEAS enzyme provided a strain proficient in beauvericin biosynthesis. Comparative infection assays with a BbBEAS knockout B. bassiana strain against three insect hosts revealed that beauvericin plays a highly significant but not indispensable role in virulence.
Xu
Yuquan
Y
Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, The University of Arizona, 250 E. Valencia Road, Tucson, AZ 85706-6800, USA.
Orozco
Rousel
R
Wijeratne
E M Kithsiri
EM
Gunatilaka
A A Leslie
AA
Stock
S Patricia
SP
Molnár
István
I
D000818:Animals; D052982:Beauveria / Q000737:chemistry / Q000378:metabolism* / Q000472:pathogenicity*; D047630:Depsipeptides / Q000096:biosynthesis* / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D007313:Insecta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis* / Q000737:chemistry
D047630:Depsipeptides; D005656:Fungal Proteins; D037521:Virulence Factors; C004456:beauvericin