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快乐十分模拟投注器:Genome mining and biosynthesis of a polyketide from a biofertilizer fungus that can facilitate reductive iron assimilation in plant
广东快乐十分投注下载 www.hmclip.net Edited by Chaitan Khosla, Stanford University, Stanford, CA, and accepted by Editorial Board Member Stephen J. Benkovic February 11, 2019 (received for review November 22, 2018)
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Extensively used as a biofertilizer in agriculture, Trichoderma harzianum t-22 has been shown to promote plant fitness via secreting small molecules that have diverse functions. Tricholignan A, discovered via genome mining in this work, is a redox-active ortho-hydroquinone natural product that can facilitate reductive Fe assimilation in plant. The biosynthesis of the ortho-hydroquinone structure by a pair of polyketide synthases (PKSs) requires a critical Cα-methylation step that serves as the programming checkpoint. The responsible standalone methyltransferase requires chaperoning by a fused and inactive acyl carrier protein for activity. The use of an inactive carrier protein to regulate PKS function adds another layer of complexity to this already highly enigmatic family of enzymes.
Fungi have the potential to produce a large repertoire of bioactive molecules, many of which can affect the growth and development of plants. Genomic survey of sequenced biofertilizer fungi showed many secondary metabolite gene clusters are anchored by iterative polyketide synthases (IPKSs), which are multidomain enzymes noted for generating diverse small molecules. Focusing on the biofertilizer Trichoderma harzianum t-22, we identified and characterized a cryptic IPKS-containing cluster that synthesizes tricholignan A, a redox-active ortho-hydroquinone. Tricholignan A is shown to reduce Fe(III) and may play a role in promoting plant growth under iron-deficient conditions. The construction of tricholignan by a pair of collaborating IPKSs was investigated using heterologous reconstitution and biochemical studies. A regioselective methylation step is shown to be a key step in formation of the ortho-hydroquinone. The responsible methyltransferase (MT) is fused with an N-terminal pseudo-acyl carrier protein (ψACP), in which the apo state of the ACP is essential for methylation of the growing polyketide chain. The ψACP is proposed to bind to the IPKS and enable the trans MT to access the growing polyketide. Our studies show that a genome-driven approach to discovering bioactive natural products from biofertilizer fungi can lead to unique compounds and biosynthetic knowledge.
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Author contributions: M.C. and Y.T. designed research; M.C., Q.L., and A.E.Y. performed research; M.C., Q.L., S.-S.G., S.E.J., and Y.T. analyzed data; and M.C. and Y.T. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. C.K. is a guest editor invited by the Editorial Board.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1819998116/-/DCSupplemental.
Published under the PNAS license.