Biosynthesis of Methoxymalonyl-acyl Carrier Protein (ACP) as an Extender Unit for Bafilomycin Polyketide in Streptomyces griseus DSM 2608

Hanh, Nguyen Phan Kieu; Hwang, Jong Yeon; Nam, Doo Hyun

doi:10.1007/s12257-018-0427-x

Cited by 6 publications

(5 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both enzyme genes are encoded in concanamycin BGC [17] and are proposed to be involved in the biosynthesis of EtMal‐CoA. The MeOMal‐ACP pathway in bafilomycin biosynthesis has been reconstituted in vitro [28] . Thus, the glyceryl‐ACP synthase VsmL likely uses 1,3‐bisphospho‐ D ‐glycerate as a substrate, transferring glycerate onto the ACP VsmJ with the release of two inorganic phosphates.…”

Section: Resultsmentioning

confidence: 99%

“…The MeOMal-ACP pathway in bafilomycin biosynthesis has been reconstituted in vitro. [28] Thus, the glyceryl-ACP synthase VsmL likely uses 1,3bisphospho-D-glycerate as a substrate, transferring glycerate onto the ACP VsmJ with the release of two inorganic phosphates. The generated glyceryl-VsmJ appears to be oxidized by glyceryl-ACP dehydrogenase VsmI and 3-oxoacyl-ACP dehydrogenase VsmK to give 2-hydroxymalonyl-VsmJ, which is then methylated by the 2-hydroxymalonyl-ACP Omethyltransferase VsmM to yield MeOMal-VsmJ.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Acyltransferase Domain Exchange between Two Independent Type I Polyketide Synthases in the Same Producer Strain of Macrolide Antibiotics

et al. 2023

View full text Add to dashboard Cite

Streptomyces graminofaciens A-8890 produces two macrolide antibiotics, FD-891 and virustomycin A, both of which show significant biological activity. In this study, we identified the virustomycin A biosynthetic gene cluster, which encodes type I polyketide synthases (PKSs), ethylmalonyl-CoA biosynthetic enzymes, methoxymalony-acyl carrier protein biosynthetic enzymes, and post-PKS modification enzymes. Next, we demonstrated that the acyltransferase domain can be exchanged between the Vsm PKSs and the PKSs involved in FD-891 biosynthesis (Gfs PKSs), without any supply problems of the unique extender units. We exchanged the malonyltransferase domain in the loading module of Gfs PKS with the ethylmalonyltransferase domain and the methoxymalonyltransferase domain of Vsm PKSs. Consequently, the expected two-carbonelongated analog 26-ethyl-FD-891 was successfully produced with a titer comparable to FD-891 production by the wild type; however, exchange with the methoxymalonyltransferase domain did not produce any FD-891 analogs. Furthermore, 26ethyl-FD-891 showed potent cytotoxic activity against HeLa cells, like natural FD-891.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Acyltransferase Domain Exchange between Two Independent Type I Polyketide Synthases in the Same Producer Strain of Macrolide Antibiotics

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Other predicted candidate genes found clustered within 25 kb of the BKR homolog also have interesting putative functions relating to polyketide and FA synthesis. Proteins containing the fkbH domain are associated with the formation of glyceryl-ACP, where they function as part of a larger protein cluster involved in the synthesis of methoxymalonyl-ACP polyketide extender units 73 , 74 . TLC (TRAM/LAG1/CLN8) lipid-sensing domain-containing proteins are associated with several functions including acyl-CoA-dependent ceramide synthesis 75 and lipid transfer 76 .…”

Section: Discussionmentioning

confidence: 99%

An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis

Welling

Лю

Kretzschmar

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Cannabis produces a class of isoprenylated resorcinyl polyketides known as cannabinoids, a subset of which are medically important and exclusive to this plant. The cannabinoid alkyl group is a critical structural feature that governs therapeutic activity. Genetic enhancement of the alkyl side-chain could lead to the development of novel chemical phenotypes (chemotypes) for pharmaceutical end-use. However, the genetic determinants underlying in planta variation of cannabinoid alkyl side-chain length remain uncharacterised. Using a diversity panel derived from the Ecofibre Cannabis germplasm collection, an extreme-phenotype genome-wide association study (XP-GWAS) was used to enrich for alkyl cannabinoid polymorphic regions. Resequencing of chemotypically extreme pools revealed a known cannabinoid synthesis pathway locus as well as a series of chemotype-associated genomic regions. One of these regions contained a candidate gene encoding a β-keto acyl carrier protein (ACP) reductase (BKR) putatively associated with polyketide fatty acid starter unit synthesis and alkyl side-chain length. Association analysis revealed twenty-two polymorphic variants spanning the length of this gene, including two nonsynonymous substitutions. The success of this first reported application of XP-GWAS for an obligate outcrossing and highly heterozygote plant genus suggests that this approach may have generic application for other plant species.

show abstract

Section: Vioprolidesmentioning

confidence: 93%

“…Afterwards, BafAIV tethers the glyceryl group on the active holo-ACP protein for the formation of glyceryl-ACP. 26 Almost at the same time, the cis FkbH-like domain in VioA was affirmed for an identical function to dephosphorylate 1,3-BPG and upload the glyceryl moiety on PCP. 24 Vioprolides include several non-proteinogenic amino acids, such as dehydrobutyrine (Dhb) and pipecolic acid stemming from threonine and lysine, respectively.…”

Section: Reviewmentioning

confidence: 93%

Biosyntheses of azetidine-containing natural products

Pang,

Yao,

Gao

et al. 2023

Org. Biomol. Chem.

View full text Add to dashboard Cite

show abstract

Biosynthesis of Methoxymalonyl-acyl Carrier Protein (ACP) as an Extender Unit for Bafilomycin Polyketide in Streptomyces griseus DSM 2608

Cited by 6 publications

References 27 publications

Acyltransferase Domain Exchange between Two Independent Type I Polyketide Synthases in the Same Producer Strain of Macrolide Antibiotics

Acyltransferase Domain Exchange between Two Independent Type I Polyketide Synthases in the Same Producer Strain of Macrolide Antibiotics

An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis

Biosyntheses of azetidine-containing natural products

Contact Info

Product

Resources

About