Genome mining and molecular characterization of the biosynthetic gene cluster of a diterpenic meroterpenoid, 15-deoxyoxalicine B, in Penicillium canescens

Yaegashi, Junko; Romsdahl, Jillian; Chiang, Yun‐Wei; Wang, Clay C. C.

doi:10.1039/c5sc01965f

Cited by 32 publications

(52 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Molecular genetic manipulations in A. terreus and P. canescens including protoplasting and gene targeting were carried out as previously described (Guo et al, 2014;Yaegashi et al, 2015). Deletions were confirmed by diagnostic PCR.…”

Section: Methodsmentioning

confidence: 99%

Discovery of McrA, a master regulator of Aspergillus secondary metabolism

Oakley

Ahuja

Sun

et al. 2016

Molecular Microbiology

Self Cite

View full text Add to dashboard Cite

Summary Fungal secondary metabolites (SMs) are extremely important in medicine and agriculture, but regulation of their biosynthesis is incompletely understood. We have developed a genetic screen in Aspergillus nidulans for negative regulators of fungal SM gene clusters and we have used this screen to isolate mutations that upregulate transcription of the non-ribosomal peptide synthetase gene required for nidulanin A biosynthesis. Several of these mutations are allelic and we have identified the mutant gene by genome sequencing. The gene, which we designate mcrA, is conserved but uncharacterized, and it encodes a putative transcription factor. Metabolite profiles of mcrA deletant, mcrA overexpressing, and parental strains reveal that mcrA regulates at least ten SM gene clusters. Deletion of mcrA stimulates SM production even in strains carrying a deletion of the SM regulator laeA, and deletion of mcrA homologs in Aspergillus terreus and Penicillum canescens alters the secondary metabolite profile of these organisms. Deleting mcrA in a genetic dereplication strain has allowed us to discover two novel compounds as well as an antibiotic not known to be produced by A. nidulans. Deletion of mcrA upregulates transcription of hundreds of genes including many that are involved in secondary metabolism, while downregulating a smaller number of genes.

show abstract

Section: Methodsmentioning

confidence: 99%

Discovery of McrA, a master regulator of Aspergillus secondary metabolism

Oakley

Ahuja

Sun

et al. 2016

Molecular Microbiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Very recently, the biosynthetic gene cluster for 15deoxyoxalicine A (35) and B (36) was discovered from the genome of Penicillium canescens (the olc cluster), and their biosyntheses were investigated by targeted gene deletions. 34 In the proposed pathway ( Fig. 3), aer the formation of 17 in the same way as that for pyripyropene A (9), 17 is geranylgeranylated by the UbiA-like PTase OlcH to yield 37.…”

Section: Biosynthesis Of 15-deoxyoxalicinesmentioning

confidence: 99%

Biosynthesis of fungal meroterpenoids

2016

View full text Add to dashboard Cite

Covering: up to September 2015. Meroterpenoids are hybrid natural products that partially originate from the terpenoid pathway. The meroterpenoids derived from fungi display quite diverse structures, with a wide range of biological properties. This review summarizes the molecular bases for their biosyntheses, which were recently elucidated with modern techniques, and also discusses the plausible biosynthetic pathways of other related natural products lacking genetic information. (Complementary to the coverage of literature by Geris and Simpson in Nat. Prod. Rep., 2009, 26, 1063-1094.).

show abstract

“…483–487 695 produced from A. fumigatus is one of the strongest acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor, and is a potential antihypercholesterolemia drug. 484 The polyketide building block, 4-hydroxy-6-(3-pyridinyl)-2H-pyran-2-one (HPPO) is synthesized by a nonreducing polyketide synthase, using nicotinyl-CoA as the start unit.…”

Section: Cyclization Via Epoxidationmentioning

confidence: 99%

“…In the oxalicine and decaturin pathways, more oxidative rearrangements are responsible for the spirocycle formation. 487 …”

Section: Cyclization Via Epoxidationmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

View full text Add to dashboard Cite

Oxidative cyclizations are important transformations that occur widely during natural product biosynthesis. The transformations from acyclic precursors to cyclized products can afford morphed scaffolds, structural rigidity and biological activities. Some of the most dramatic structural alterations in natural product biosynthesis occur through oxidative cyclization. In this review, we examine the different strategies used by Nature to create new intra-(inter-)-molecular bonds via redox chemistry. The review will cover both oxidation- and reduction-enabled cyclization mechanisms, with an emphasis on the former. Radical cyclizations catalyzed by P450, nonheme iron, α-KG dependent oxygenases and radical SAM enzymes are discussed to illustrate the use of molecular oxygen and S-adenosylmethionine to forge new bonds at unactivated sites via one-electron manifolds. Nonradical cyclizations catalyzed by flavin-dependent monooxygenases and NAD(P)H-dependent reductases are covered to show the use of two-electron manifolds in initiating cyclization reactions. The oxidative installation of epoxides and halogens into acyclic scaffolds to drive subsequent cyclizations are separately discussed as examples of “disappearing” reactive handles. Lastly, oxidative rearrangement of rings systems, including contractions and expansions will be covered.

show abstract

Genome mining and molecular characterization of the biosynthetic gene cluster of a diterpenic meroterpenoid, 15-deoxyoxalicine B, in Penicillium canescens

Abstract: The biosynthetic pathway of a diterpenic meroterpenoid was elucidated by combination of genome mining, gene targeting, and natural product chemistry.

Cited by 32 publications

References 32 publications

Discovery of McrA, a master regulator of Aspergillus secondary metabolism

Discovery of McrA, a master regulator of Aspergillus secondary metabolism

Biosynthesis of fungal meroterpenoids

Oxidative Cyclization in Natural Product Biosynthesis

Contact Info

Product

Resources

About