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Dalmanol biosyntheses require coupling of two separate polyketide gene clusters.

ABSTRACT: Polyketide-polyketide hybrids are unique natural products with promising bioactivity, but the hybridization processes remain poorly understood. Herein, we present that the biosynthetic pathways of two immunosuppressants, dalmanol A and acetodalmanol A, result from an unspecific monooxygenase triggered hybridization of two distinct polyketide (naphthalene and chromane) biosynthetic gene clusters. The orchestration of the functional dimorphism of the polyketide synthase (ChrA) ketoreductase (KR) domain (shortened as ChrA KR) with that of the KR partner (ChrB) in the bioassembly line increases the polyketide diversity and allows the fungal generation of plant chromanes (e.g., noreugenin) and phloroglucinols (e.g., 2,4,6-trihydroxyacetophenone). The simultaneous fungal biosynthesis of 1,3,6,8- and 2-acetyl-1,3,6,8-tetrahydroxynaphthalenes was addressed as well. Collectively, the work may symbolize a movement in understanding the multiple-gene-cluster involved natural product biosynthesis, and highlights the possible fungal generations of some chromane- and phloroglucinol-based phytochemicals.

SUBMITTER: Zhou ZZ

PROVIDER: S-EPMC6335865 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Dalmanol biosyntheses require coupling of two separate polyketide gene clusters.

Zhou Zhen Zhen ZZ Zhu Hong Jie HJ Lin Li Ping LP Zhang Xuan X Ge Hui Ming HM Jiao Rui Hua RH Tan Ren Xiang RX

Chemical science 20181127 1

Polyketide-polyketide hybrids are unique natural products with promising bioactivity, but the hybridization processes remain poorly understood. Herein, we present that the biosynthetic pathways of two immunosuppressants, dalmanol A and acetodalmanol A, result from an unspecific monooxygenase triggered hybridization of two distinct polyketide (naphthalene and chromane) biosynthetic gene clusters. The orchestration of the functional dimorphism of the polyketide synthase (ChrA) ketoreductase (KR) d ...[more]

PMID: 30746075

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Project description:Mycosphaerella fijiensis, causal agent of black Sigatoka disease of banana, is a Dothideomycete fungus closely related to fungi that produce polyketides important for plant pathogenicity. We utilized the M. fijiensis genome sequence to predict PKS genes and their gene clusters and make bioinformatics predictions about the types of compounds produced by these clusters. Eight PKS gene clusters were identified in the M. fijiensis genome, placing M. fijiensis into the 23rd percentile for the number of PKS genes compared to other Dothideomycetes. Analysis of the PKS domains identified three of the PKS enzymes as non-reducing and two as highly reducing. Gene clusters contained types of genes frequently found in PKS clusters including genes encoding transporters, oxidoreductases, methyltransferases, and non-ribosomal peptide synthases. Phylogenetic analysis identified a putative PKS cluster encoding melanin biosynthesis. None of the other clusters were closely aligned with genes encoding known polyketides, however three of the PKS genes fell into clades with clusters encoding alternapyrone, fumonisin, and solanapyrone produced by Alternaria and Fusarium species. A search for homologs among available genomic sequences from 103 Dothideomycetes identified close homologs (>80% similarity) for six of the PKS sequences. One of the PKS sequences was not similar (< 60% similarity) to sequences in any of the 103 genomes, suggesting that it encodes a unique compound. Comparison of the M. fijiensis PKS sequences with those of two other banana pathogens, M. musicola and M. eumusae, showed that these two species have close homologs to five of the M. fijiensis PKS sequences, but three others were not found in either species. RT-PCR and RNA-Seq analysis showed that the melanin PKS cluster was down-regulated in infected banana as compared to growth in culture. Three other clusters, however were strongly upregulated during disease development in banana, suggesting that they may encode polyketides important in pathogenicity.

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Dalmanol biosyntheses require coupling of two separate polyketide gene clusters.

Publications

Dalmanol biosyntheses require coupling of two separate polyketide gene clusters.

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