Biosynthesis of fungal indole alkaloids

Xu, Wei; Gavia, Diego J.; Tang, Yi

doi:10.1039/c4np00073k

Cited by 186 publications

(120 citation statements)

References 104 publications

(217 reference statements)

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…Many other compounds produced by ascomycetes are toxic and are known as mycotoxins, which pose substantial threats to human food supplies and health (5). Major classes of natural products from Ascomycetes include alkaloids (6,7), terpenoids (8), polyketides (PKs) (9)(10)(11)(12), nonribosomal peptides (NRPs) (12)(13)(14), and PK-NRP hybrids (15,16). However, ribosomally synthesized and posttranslationally modified peptides (RiPPs), a rapidly growing class of natural products (17), have rarely been found in Ascomycetes.…”

mentioning

confidence: 99%

Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes

Ding

Liu

Jia

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

Production of ribosomally synthesized and posttranslationally modified peptides (RiPPs) has rarely been reported in fungi, even though organisms of this kingdom have a long history as a prolific source of natural products. Here we report an investigation of the phomopsins, antimitotic mycotoxins. We show that phomopsin is a fungal RiPP and demonstrate the widespread presence of a pathway for the biosynthesis of a family of fungal cyclic RiPPs, which we term dikaritins. We characterize PhomM as an S-adenosylmethioninedependent α-N-methyltransferase that converts phomopsin A to an N,N-dimethylated congener (phomopsin E), and show that the methyltransferases involved in dikaritin biosynthesis have evolved differently and likely have broad substrate specificities. Genome mining studies identified eight previously unknown dikaritins in different strains, highlighting the untapped capacity of RiPP biosynthesis in fungi and setting the stage for investigating the biological activities and unknown biosynthetic transformations of this family of fungal natural products.RiPP | mycotoxin | posttranslational modification | methyltransferase | biosynthesis

show abstract

mentioning

confidence: 99%

Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes

Ding

Liu

Jia

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

show abstract

“…Although early success stories focused on PKs and NRPs primarily from actinomycete bacteria, combinatorial biosynthesis has since been applied to many classes of natural products, including RIPPs 92 , saccharides 93 , terpenoids 94 and alkaloids 95 from assorted organisms. Because the non-modular biosynthetic machineries for these natural products are more amenable for combinatorial assembly than PKS and NRPS systems, they have huge potential to generate combinatorial biosynthetic libraries.…”

Section: Perspectivementioning

confidence: 99%

Reinvigorating natural product combinatorial biosynthesis with synthetic biology

2015

View full text Add to dashboard Cite

Natural products continue to play a pivotal role in drug discovery efforts and in understanding human health. The ability to extend nature’s chemistry through combinatorial biosynthesis – altering functional groups, regiochemistry, and scaffold backbones through manipulation of biosynthetic enzymes – offers unique opportunities to create natural product analogues. Incorporating emerging synthetic biology techniques has the potential to further accelerate the refinement of combinatorial biosynthesis as a robust platform for the diversification of natural chemical drug leads. Two decades after the field originated, we discuss the current limitations, realities, and the state of the art of combinatorial biosynthesis, including the engineering of substrate specificity of biosynthetic enzymes and the development heterologous expression systems for biosynthetic pathways. We also propose a new perspective for the combinatorial biosynthesis of natural products that could reinvigorate drug discovery by using synthetic biology in combination with synthetic chemistry.

show abstract

“…[1] Indole diketopiperazine alkaloids, belonging to the diketopiperazine alkaloids family, are a special subclass of indole alkaloids. [1] Indole diketopiperazine alkaloids, belonging to the diketopiperazine alkaloids family, are a special subclass of indole alkaloids.…”

Section: Introductionmentioning

confidence: 99%

Three New Indole Diketopiperazine Alkaloids from Aspergillus ochraceus

Wen

Liu

Zhang

et al. 2018

Chemistry & Biodiversity

View full text Add to dashboard Cite

Asperochramides A - D (1 - 4), a new natural product and three new indole diketopiperazine alkaloids, along with seven known analogs (5 - 11), were isolated from the ethyl acetate extract of Aspergillus ochraceus. Their structures were elucidated by extensive spectroscopic analyses, ECD calculation, and single-crystal X-ray diffraction analysis. Compounds 3 and 4 represent a rare group of indole diketopiperazine alkaloid with a 3-hydroxyl-2-indolone moiety. The in vitro anti-inflammatory effects of compounds 1 and 3 - 11 were investigated by using LPS-stimulated murine macrophage RAW 264.7 cells. Compounds 1, 8, 10, and 11 showed potential anti-inflammatory activities.

show abstract

Biosynthesis of fungal indole alkaloids

Cited by 186 publications

References 104 publications

Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes

Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes

Reinvigorating natural product combinatorial biosynthesis with synthetic biology

Three New Indole Diketopiperazine Alkaloids from Aspergillus ochraceus

Contact Info

Product

Resources

About