Issue 5, 2011

The programming role of trans-acting enoyl reductases during the biosynthesis of highly reduced fungal polyketides

Abstract

A novel polyketide synthase nonribosomal peptide synthetase (PKS-NRPS) genecluster was isolated from Beauveria bassiania 992.05. The cluster encodes the enzymes responsible for the biosynthesis of the new 2-pyridone desmethylbassianin (DMB). DMB is structurally related to tenellin from B. bassiana 110.25 but it differs in chain length and degree of methylation. Despite these programming differences the 20 kb DMB biosynthetic genecluster has 90% sequence identity to the tenellingenecluster. Silencing of the PKS-NRPS gene, dmbS, resulted in total loss of DMB production. Co-expression of dmbS in Aspergillus oryzae with its cognate trans-actingenoyl reductase gene, dmbC, produced predesmethylbassianin A, the first isolable precursor in the biosynthetic pathway. Expression of dmbS with the tenellintrans-actingenoyl reductase gene, tenC, also resulted in the production of predesmethylbassianin A. Co-expression of tenS, the tenellin PKS-NRPS, with dmbC produced pretenellin A. These results show that the tenS and dmbS encoded PKS-NRPS contains the programme for polyketide biosynthesis, while the trans-actingERs appear to control the fidelity of the programme. Expression of a hybrid synthetase in which the PKS of the tenellin synthetase was fused to the NRPS from DMBS produced prototenellins A to C, indicating that the NRPS does not act as a selecting gatekeeper to affect the PKS programme.

Graphical abstract: The programming role of trans-acting enoyl reductases during the biosynthesis of highly reduced fungal polyketides

Supplementary files

Article information

Article type
Edge Article
Submitted
14 Jan 2011
Accepted
11 Feb 2011
First published
02 Mar 2011

Chem. Sci., 2011,2, 972-979

The programming role of trans-acting enoyl reductases during the biosynthesis of highly reduced fungal polyketides

M. N. Heneghan, A. A. Yakasai, K. Williams, K. A. Kadir, Z. Wasil, W. Bakeer, K. M. Fisch, A. M. Bailey, T. J. Simpson, R. J. Cox and C. M. Lazarus, Chem. Sci., 2011, 2, 972 DOI: 10.1039/C1SC00023C

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