Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis

Awodi, Ufedo R.; Ronan, Jade L.; Masschelein, Joleen; Santos, Emmanuel L. C. de los; Challis, Gregory L.

doi:10.1039/c6sc02803a

Cited by 50 publications

(78 citation statements)

References 33 publications

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“…Most alkaloids are amino acid derivatives, but they can also be synthesized via terpenoids, as in the case of steroidal alkaloids, or formed from polyketide pathways . Each case, using a different mechanism to introduce the nitrogen atom, but the amino acid mechanism is most common …”

Section: Chemistrymentioning

confidence: 99%

“…147 Most alkaloids are amino acid derivatives, but they can also be synthesized via terpenoids, as in the case of steroidal alkaloids, 148 or formed from polyketide pathways. [149][150][151] Each case, using a different mechanism to introduce the nitrogen atom, but the amino acid mechanism is most common. [152][153][154] Production of these natural products, and their composition and quantity in plants vary with the diurnal cycle.…”

Section: Allelochemicals Containing a Nitrogen Atommentioning

confidence: 99%

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Recent advances in allelopathy for weed control: from knowledge to applications

Macías

Mejías

Molinillo

2019

Pest Management Science

210

131

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Allelopathy is the biological phenomenon of chemical interactions between living organisms in the ecosystem, and must be taken into account in addressing pest and weed problems in future sustainable agriculture. Allelopathy is a multidisciplinary science, but in some cases, aspects of its chemistry are overlooked, despite the need for a deep knowledge of the chemical structural characteristics of allelochemicals to facilitate the design of new herbicides. This review is focused on the most important advances in allelopathy, paying particular attention to the design and development of phenolic compounds, terpenoids and alkaloids as herbicides. The isolation of allelochemicals is mainly addressed, but other aspects such as the analysis and activities of derivatives or analogs are also covered. Furthermore, the use of allelopathy in the fight against parasitic plants is included. The past 12 years have been a prolific period for publications on allelopathy. This critical review discusses future research areas in this field and the state of the art is analyzed from the chemist's perspective. © 2019 Society of Chemical Industry

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Section: Chemistrymentioning

confidence: 99%

Section: Allelochemicals Containing a Nitrogen Atommentioning

confidence: 99%

Recent advances in allelopathy for weed control: from knowledge to applications

Macías

Mejías

Molinillo

2019

Pest Management Science

210

131

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“…Intrigued by these compounds, which exhibit potent 55 antibacterial activity, and as part of studies to decipher their biosynthetic pathway, we 56 employed targeted metabolomics to identify further congeners that may have been missed 57 during manual analysis of culture extracts. This led us to identify the formicapyridines (1)(2)(3)(4)(5)(6)(7)(8)(9), 58 pyridine containing polyketide alkaloids which represent additional products of the 59 are minor shunt metabolites that likely arise due to derailment of the formicamycin 70 biosynthetic pathway. Intrigued by these observations we investigated the possibility of 71 reprogramming, or evolving, the BGC such that the formicapyridines might become the 72 major products of the formicamycin BGC.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the methyl group atom C24 shows 218 enrichment and coupling to C1. The C2 atom of [1,[2][3][4][5][6][7][8][9][10][11][12][13] C2] sodium acetate is highlighted as a 219 blue circle, the C1 atom as a black circle, and the coupled unit by a bold line. The gene product ForD shows significant sequence similarity to aromatase/cyclases 238 (ARO/CYC) such as the N-terminal domain (pfam 03364) of the archetypical tetracenomycin 239 polyketide cyclase TcmN which belongs to the Bet v1-like superfamily (cl10022) 15 .…”

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confidence: 99%

Aromatic polyketide biosynthesis: fidelity, evolution and engineering

Qin

Devine²,

Hutchings³

et al. 2019

Preprint

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14We report the formicapyridines which are structurally and biosynthetically related to the 15 pentacyclic fasamycin and formicamycin aromatic polyketides but comprise a rare pyridine 16 moiety. These new compounds are trace level metabolites formed by derailment of the major 17 biosynthetic pathway. Inspired by evolutionary logic we show that rational mutation of a 18 single gene in the biosynthetic gene cluster leads to a significant increase both in total 19 formicapyridine production and their enrichment relative to the fasamycins/formicamycins. 20Our observations broaden the polyketide biosynthetic landscape and identify a non-catalytic 21 role for ABM superfamily proteins in type II polyketide synthase assemblages for maintaining 22 biosynthetic pathway fidelity. 23 24 formicamycin (for) biosynthetic gene cluster (BGC). Products of type II PKS systems which 60 contain a pyridine moiety are extremely rare 7 . 61 62 Figure 1 | Chemical structures of metabolites isolated from Streptomyces formicae. 63Compounds 1-9 and 13 were discovered during this study whereas 10-12 and 14-26 were 64 reported in an earlier study 5 . 65Challis and co-workers recently showed that the majority of actinomycete derived polyketide 66 alkaloids, including those containing a pyridine moiety, arise from reactive intermediates 67 formed after transamination of aldehydes generated from reductive off-loading of the 68

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“…With our studies on the biosynthesis of coelimycin P1 and reports on the biosynthesis of other polyketide alkaloids, we hypothesized that polyketide alkaloid biosynthesis in actinobacteria go through universal steps; specifically, reductive chain release and transamination 5 . We queried Genbank and Refseq databases with the following search list: This search finds stretches of DNA that contain at least two polyketide modules one of which containing a reductive chain release domain, near transaminase gene.…”

Section: Polyketide Alkaloidsmentioning

confidence: 99%

clusterTools: proximity searches for functional elements to identify putative biosynthetic gene clusters

Santos

Challis

2017

Preprint

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Motivation: The low cost of DNA sequencing has accelerated research in natural product biosynthesis allowing us to rapidly link small molecules to the clusters that produce them. However, the large amount of data means that the number of putative biosynthetic gene clusters (BGCs) far exceeds our ability to experimentally characterize them. This necessitates the need for development of further tools to analyze putative BGCs to flag those of interest for further characterization. Results: clusterTools implements a framework to aid in the characterization of putative BGCs. It does this by organizing genomic information on coding sequences in a way that enables directed, hypothesis-driven queries for functional elements in close physical proximity of each other. Genomic sequence databases can be constructed in clusterTools with an interface to the NCBI Genbank and Genomes databases, or from private sequence databases. clusterTools can be used either to identify interesting BGCs from a database of putative BGCs, or on databases of genomic sequences to identify and download regions of interest in the DNA for further processing and annotation in programs such as antiSMASH. We have used clusterTools to identify putative and known biosynthetic gene clusters involved in bacterial polyketide alkaoloid and tetronate biosynthesis.

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Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis

Abstract: Polyketide synthase reductive chain release and subsequent transamination are key steps in the biosynthesis of polyketide alkaloids in actinobacteria.

Cited by 50 publications

References 33 publications

Recent advances in allelopathy for weed control: from knowledge to applications

Recent advances in allelopathy for weed control: from knowledge to applications

Aromatic polyketide biosynthesis: fidelity, evolution and engineering

clusterTools: proximity searches for functional elements to identify putative biosynthetic gene clusters

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