Cytochrome P450 enzymes in fungal natural product biosynthesis

Zhang, Xingwang; Guo, Jiawei; Cheng, Fangyuan; Li, Shengying

doi:10.1039/d1np00004g

Cited by 130 publications

(100 citation statements)

References 197 publications

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“…Since most bacterial and fungal P450s are cytosolic and soluble, these variants are better suited for biotechnology applications compared to their membrane-bound plant and mammalian homologs (Distefano et al 2021;Finnigan et al 2020;Iizaka et al 2021;Toplak et al 2021;Zhang et al 2021b). In P. megaterium a number of different P450 enzymes were found.…”

Section: Secretion Of Recombinant Proteins With P Megateriummentioning

confidence: 99%

The “beauty in the beast”—the multiple uses of Priestia megaterium in biotechnology

Biedendieck

Knuuti

Jahn

2021

Appl Microbiol Biotechnol

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Over 30 years, the Gram-positive bacterium Priestia megaterium (previously known as Bacillus megaterium) was systematically developed for biotechnological applications ranging from the production of small molecules like vitamin B12, over polymers like polyhydroxybutyrate (PHB) up to the in vivo and in vitro synthesis of multiple proteins and finally whole-cell applications. Here we describe the use of the natural vitamin B12 (cobalamin) producer P. megaterium for the elucidation of the biosynthetic pathway and the subsequent systematic knowledge-based development for production purposes. The formation of PHB, a natural product of P. megaterium and potential petro-plastic substitute, is covered and discussed. Further important biotechnological characteristics of P. megaterium for recombinant protein production including high protein secretion capacity and simple cultivation on value-added carbon sources are outlined. This includes the advanced system with almost 30 commercially available expression vectors for the intracellular and extracellular production of recombinant proteins at the g/L scale. We also revealed a novel P. megaterium transcription-translation system as a complementary and versatile biotechnological tool kit. As an impressive biotechnology application, the formation of various cytochrome P450 is also critically highlighted. Finally, whole cellular applications in plant protection are completing the overall picture of P. megaterium as a versatile giant cell factory. Key points • The use of Priestia megaterium for the biosynthesis of small molecules and recombinant proteins through to whole-cell applications is reviewed. • P. megaterium can act as a promising alternative host in biotechnological production processes.

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Section: Secretion Of Recombinant Proteins With P Megateriummentioning

confidence: 99%

The “beauty in the beast”—the multiple uses of Priestia megaterium in biotechnology

Biedendieck

Knuuti

Jahn

2021

Appl Microbiol Biotechnol

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“…Typical SM gene clusters contain a key pathway gene, coding for a PKS, a NRPS, or a terpene cyclase, which is often easily identified by its larger size. They also contain genes for other modifying enzymes frequently belonging to easily recognizable families, e.g., P450 monooxygenases [59], and in some cases genes for permeases involved in their excretion. SM biosynthetic pathways can be controlled by specific regulatory genes [60] frequently belonging to the Zn cluster family and normally included in the corresponding cluster.…”

Section: Genetic Organization and Regulation Of Sm Genesmentioning

confidence: 99%

Fungal Secondary Metabolism

Ávalos

Limón

2021

Encyclopedia

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Fungal secondary metabolites (SMs) comprise a vast collection of compounds expendable for these organisms under laboratory conditions. They exhibit enormous chemical diversity, and usually belong to four major families: terpenoids, polyketides, non-ribosomal peptides, or a combination of the last two. Their functions are very diverse and are normally associated with a greater fitness of the producing fungi in their environment, which often compete with other microorganisms or interact with host plants. Many SMs have beneficial applications, e.g., as antibiotics or medical drugs, but others, known as mycotoxins, are harmful to health.

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“…Cytochrome P450s (CYPs) are very common in fungal natural product pathways, 69,70 however, only 33 % of maleidride BGCs contain a CYP (excluding orthologous BGCs). In general CYP enzymes have low sequence identity, but show structural similarities, and have four characteristic conserved motifs, involved in heme and oxygen-binding.…”

Section: Cytochrome P450mentioning

confidence: 99%

In silico analyses of maleidride biosynthetic gene clusters

Williams

Mattos-Shipley

Willis

et al. 2021

Preprint

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Maleidrides are a family of structurally related fungal natural products, many of which possess diverse, potent bioactivities. Previous identification of several maleidride biosynthetic gene clusters, and subsequent experimental work, has determined the ‘core’ set of genes required to construct the characteristic medium-sized alicyclic ring with maleic anhydride moieties. Through genome mining, this work has used these core genes to discover ten entirely novel maleidride biosynthetic gene clusters, amongst both publicly available genomes, and encoded within the genome of the previously un-sequenced epiheveadride producer Wicklowia aquatica CBS125634. We have undertaken phylogenetic analyses and comparative bioinformatics on all known and putative maleidride biosynthetic gene clusters to gain further insights regarding these unique biosynthetic pathways.

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Cytochrome P450 enzymes in fungal natural product biosynthesis

Abstract: P450s play crucial roles in fungal natural product biosynthesis by mediating various common and uncommon reactions.

Cited by 130 publications

References 197 publications

The “beauty in the beast”—the multiple uses of Priestia megaterium in biotechnology

The “beauty in the beast”—the multiple uses of Priestia megaterium in biotechnology

Fungal Secondary Metabolism

In silico analyses of maleidride biosynthetic gene clusters

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