Structural analysis of SgvP involved in carbon–sulfur bond formation during griseoviridin biosynthesis

Qin, Liqiang; Chen, Yan; Zhang, Guiqin; Zhang, Huaidong

doi:10.1002/1873-3468.12643

Cited by 9 publications

(8 citation statements)

References 38 publications

(49 reference statements)

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“…30 The role of this natural product or intermediate is not clear, but deletion of the CYP154A1-encoding gene compromised the stability of the bacterial spores of the producing strain. 30 Three additional structures of P450s from Streptomyces , StaF (PDB ID: 5EX8), 106 SgvP (4MM0), 189 and CYP105P2 (5IT1), 190 revealed that their heme groups also adopt this unusual flipped orientation (Fig. 8A).…”

Section: Structurementioning

confidence: 99%

Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function

et al. 2017

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Cytochrome P450 enzymes (P450s) are some of the most exquisite and versatile biocatalysts found in nature. In addition to their well-known roles in steroid biosynthesis and drug metabolism in humans, P450s are key players in natural product biosynthetic pathways. Natural products, the most chemically and structurally diverse small molecules known, require an extensive collection of P450s to accept and functionalize their unique scaffolds. In this review, we survey the current catalytic landscape of P450s within the Streptomyces genus, one of the most prolific producers of natural products, and comprehensively summarize the functionally characterized P450s from Streptomyces. A sequence similarity network of >8500 P450s revealed insights into the sequence–function relationships of these oxygen-dependent metalloenzymes. Although only ~2.4% and <0.4% of streptomycete P450s have been functionally and structurally characterized, respectively, the study of streptomycete P450s involved in the biosynthesis of natural products has revealed their diverse roles in nature, expanded their catalytic repertoire, created structural and mechanistic paradigms, and exposed their potential for biomedical and biotechnological applications. Continued study of these remarkable enzymes will undoubtedly expose their true complement of chemical and biological capabilities.

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Section: Structurementioning

confidence: 99%

Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function

et al. 2017

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“…184 A P450 (SgvP) has been implicated in the synthesis of this thioether bridge, 185,186 with gene disruption experiments showing the essential nature of this P450 in thioether formation (Fig. 17D).…”

mentioning

confidence: 99%

Unrivalled diversity: the many roles and reactions of bacterial cytochromes P450 in secondary metabolism

et al. 2018

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The cytochromes P450 (P450s) are a superfamily of heme-containing monooxygenases that perform diverse catalytic roles in many species, including bacteria. The P450 superfamily is widely known for the hydroxylation of unactivated C-H bonds, but the diversity of reactions that P450s can perform vastly exceeds this undoubtedly impressive chemical transformation. Within bacteria, P450s play important roles in many biosynthetic and biodegradative processes that span a wide range of secondary metabolite pathways and present diverse chemical transformations. In this review, we aim to provide an overview of the range of chemical transformations that P450 enzymes can catalyse within bacterial secondary metabolism, with the intention to provide an important resource to aid in understanding of the potential roles of P450 enzymes within newly identified bacterial biosynthetic pathways. 1.Introduction to P450s 2.Chemistry of P450 enzymes 3.Bacterial biosynthesis pathways involving P450s 3.1Terpene metabolism 3.1. Battersby (1925Battersby ( -2018 to the molecular understanding of biosynthesis over the course of their careers.

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“…Akink of acid-alcohol pair (D/ E-T/S) in the I-helix is acommon feature in the great majority of P450s,w hich is important for dioxygen activation during the catalytic cycle. [15] However,the semi-conserved D/E near the conserved threonine (T239) is replaced by ab asic lysine residue (K238) in CxnD.A mong the microbial P450s supposed to be responsible for CÀSb ond formation in secondary metabolite biosynthesis,acrystal structure of SgvP in apo form (PDB ID 4MM0) [16] has been determined, which is rather similar to CxnD in overall structure (RSMD of 2.0 for the Ca-atoms,T able S6). Thes uperposition of SgvP and CxnD structures shows that CxnD has an extra B'-helix and acompact B-C loop compared with SgvP,inagreement with alarger cavity to accommodate the macrolactam substrate for SgvP (Figure S37).…”

Section: Resultsmentioning

confidence: 99%

The Cytochrome P450 Catalyzing C−S Bond Formation in S‐Heterocyclization of Chuangxinmycin Biosynthesis

Shi

Jiang

et al. 2021

Angew Chem Int Ed

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Microbial sulfur-containing secondary metabolites show various biological activities,but the CÀSbond-forming in their biosynthetic metabolism has not been thoroughly understood. Here,w ep resent genetic, biochemical and structural characterization of acytochrome P450 monooxygenase CxnD exhibiting C À Sbond forming activity in S-heterocyclization of chuangxinmycin biosynthesis.I nv ivo and in vitro analyses demonstrated that CxnD generated an indole-fused dihydrothiopyran skeleton from a l-Trp-derived thiol intermediate. Furthermore,X-ray crystal structure of CxnD in complex with asubstrate analogue and structure-based mutagenesis revealed intimate details of the substrate binding mode.Aradical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate was proposed for CxnD,whichprovided valuable insights into the molecular basis for the intra-molecular C(sp 2 )ÀHthiolation by the P450 in chuangxinmycin biosynthesis.

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Structural analysis of SgvP involved in carbon–sulfur bond formation during griseoviridin biosynthesis

Abstract: Coordinate and structure factor were deposited in the Protein Data Bank database under the accession number 4MM0.

Cited by 9 publications

References 38 publications

Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function

Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function

Unrivalled diversity: the many roles and reactions of bacterial cytochromes P450 in secondary metabolism

The Cytochrome P450 Catalyzing C−S Bond Formation in S‐Heterocyclization of Chuangxinmycin Biosynthesis

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