Mechanistic insights into Diels-Alder reactions in natural product biosynthesis

Hashimoto, Takuya; Kuzuyama, Tomohisa

doi:10.1016/j.cbpa.2016.09.015

Cited by 34 publications

(24 citation statements)

References 53 publications

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“…However, related PKSs have been shown to exert Diels-Alderase activity and also stand-alone Diels Alderases are known [ 60 , 61 ]. Unfortunately, the structural requirements for enzymatic Diels-Alderase activity are not sufficiently described to conclude a responsible domain and enzymes currently known to show this activity show hardly any sequence similarities [ 61 ]. Therefore it can neither be proposed nor excluded that the PKSs of the SOR cluster or TR_73623 could be required for this reaction.…”

Section: Discussionmentioning

confidence: 99%

A CRE1- regulated cluster is responsible for light dependent production of dihydrotrichotetronin in Trichoderma reesei

et al. 2017

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Changing light conditions, caused by the rotation of earth resulting in day and night or growth on the surface or within a substrate, result in considerably altered physiological processes in fungi. For the biotechnological workhorse Trichoderma reesei, regulation of glycoside hydrolase gene expression, especially cellulase expression was shown to be a target of light dependent gene regulation. Analysis of regulatory targets of the carbon catabolite repressor CRE1 under cellulase inducing conditions revealed a secondary metabolite cluster to be differentially regulated in light and darkness and by photoreceptors. We found that this cluster is involved in production of trichodimerol and that the two polyketide synthases of the cluster are essential for biosynthesis of dihydrotrichotetronine (syn. bislongiquinolide or bisorbibutenolide). Additionally, an indirect influence on production of the peptaibol antibiotic paracelsin was observed. The two polyketide synthetase genes as well as the monooxygenase gene of the cluster were found to be connected at the level of transcription in a positive feedback cycle in darkness, but negative feedback in light, indicating a cellular sensing and response mechanism for the products of these enzymes. The transcription factor TR_102497/YPR2 residing within the cluster regulates the cluster genes in a light dependent manner. Additionally, an interrelationship of this cluster with regulation of cellulase gene expression was detected. Hence the regulatory connection between primary and secondary metabolism appears more widespread than previously assumed, indicating a sophisticated distribution of resources either to degradation of substrate (feed) or to antagonism of competitors (fight), which is influenced by light.

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Section: Discussionmentioning

confidence: 99%

A CRE1- regulated cluster is responsible for light dependent production of dihydrotrichotetronin in Trichoderma reesei

et al. 2017

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“…The identification and study of naturally selected Diels-Alderases has advanced significantly in the past five years, and as a testament to the current excitement in the field, there have been no less than half-a-dozen reviews of the subject in the past year alone. 10–15 Furthermore, despite a large catalog of biosynthetic pathways hypothesized to involve an enzyme catalyzed Diels-Alder reaction, 16–18 progress in the area has proven to be quite slow.…”

Section: Introduction and Scopementioning

confidence: 99%

Natural [4 + 2]-Cyclases

et al. 2016

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[4 + 2]-Cycloadditions are increasingly being recognized in the biosynthetic pathways of many structurally complex natural products. A relatively small collection of enzymes from these pathways have been demonstrated to increase rates of cyclization and impose stereochemical constraints on the reactions. While mechanistic investigation of these enzymes is just beginning, recent studies have provided new insights with implications for understanding their biosynthetic roles, mechanisms of catalysis and evolutionary origin.

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“…This finding makes a new addition to our understanding of eremophilane sesquiterpenes. It has been demonstrated that the Diels-Alder reaction can be catalyzed by natural Diels-Alderases from microorganisms, indicating that the endophytes in roots of L. cymbulifera might be involved in the biosynthesis of 1 and 2 (Hashimoto et al, 2015; Hashimoto and Kuzuyama, 2016). The production of 1 and 2 might be the result of co-evolution of L. cymbulifera and coexisting microorganisms in an unusual environment in which they faced unusual stresses.…”

Section: Resultsmentioning

confidence: 99%

Phytotoxic Terpenoids from Ligularia cymbulifera Roots

et al. 2017

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Ligularia cymbulifera is one of the predominant species in the Hengduan Mountains, China, and has led to a decrease in the amount of forage grass in this area. However, little is known about the mechanism behind its predominance. In this study, two novel eremophilane sesquiterpenes, ligulacymirin A and B (1 and 2), together with seven other known terpenoids (3–9), were isolated from the roots of L. cymbulifera. The structures of 1 and 2 were determined by spectroscopic methods and single-crystal X-ray diffraction. Each compound showed phytotoxic activities against Arabidopsis thaliana, and each was detected and identified in rhizosphere soil by UHPLC-MS. Compound 3 was the most potent phytotoxin, showing remarkable inhibition against both seedling growth (EC50 = 30.33 ± 0.94 μg/mL) and seed germination (EC50 = 155.13 ± 0.52 μg/mL), with an average content in rhizosphere soil of 3.44 μg/g. These results indicate that terpenoids in L. cymbulifera roots might be released as phytotoxins in rhizosphere soil to interfere with neighboring plants.

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Mechanistic insights into Diels-Alder reactions in natural product biosynthesis

Cited by 34 publications

References 53 publications

A CRE1- regulated cluster is responsible for light dependent production of dihydrotrichotetronin in Trichoderma reesei

A CRE1- regulated cluster is responsible for light dependent production of dihydrotrichotetronin in Trichoderma reesei

Natural [4 + 2]-Cyclases

Phytotoxic Terpenoids from Ligularia cymbulifera Roots

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