Type II Polyketide Synthases: Gaining a Deeper Insight into Enzymatic Teamwork

Hertweck, Christian; Luzhetskyy, Andriy; Rebets, Yuri; Bechthold, Andreas

doi:10.1002/chin.200723225

Cited by 64 publications

(110 citation statements)

References 1 publication

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…SARP-like pathway-specific transcriptional activators are essential for angucycline production [4], however there is limited information on other regulatory genes within angucycline biosynthetic gene clusters. We recently showed that, besides transcriptional activator gene lanI , repressor gene lanK governs late steps of landomycins production in S. cyanogenus S136 [2].…”

Section: Discussionmentioning

confidence: 99%

Properties of lanK-based regulatory circuit involved in landomycin biosynthesis in Streptomyces cyanogenus S136

Ostash

Zhu

et al. 2010

Russ J Genet

View full text Add to dashboard Cite

LanK is TetR-like regulatory protein recently shown to regulate the export and glycosylation of landomycins in Streptomyces cyanogenus S136. Here, several properties of the lanK-mediatcd regulation were deciphered. LanK seems to function as oligomer as evident from experiments in vitro. In vivo, it is able to recognize various landomycins with altered aglycon structure and the minimal concentration of landomycin A sensed by LanK lies in low nanomolar range. Coexpression studies showed that the positive regulatory gene lanI upregulates lanK-dependent lan genes once the negative LanK-regulation is cancelled. Gene lanK can be useful for the construction of biosensor strains for sensitive and specific identification of producers of landomycin-like molecules with long glycosidic chains.The TetR family of transcriptional repressors is one of the largest groups of regulators governing various aspects of prokaryotic physiology [1]. Although all TetR-like proteins share a similar mode of action, each of them is uniquely tailored to sense and respond to the presence of specific small molecule ligands in a cellular environment. Currently, reliable in silico prediction of functions of regulatory proteins is a major challenge, emphasizing the need for experimental verification. Genes encoding putative TetR-like proteins are especially abundant in actinomycete genomes, and are particularly often found within gene clusters encoding biosyntheses of secondary metabolites. Despite this fact, there is little known on the significance and exact role of TetR-like regulators in antibiotic production.Recently we have characterized the tetR-like gene lanK involved in the biosynthesis of landomycin A in Streptomyces cyanogenus S136 [2]. Our long-term interest in landomycin biosynthesis stems from the unusual structural features and unique spectrum of bioactivities displayed by the members of landomycin family [3][4][5]. The potency of landomycins depends on the length of their carbohydrate chain; namely, landomycin A possessing the longest 1 The article is published in the original.

show abstract

Section: Discussionmentioning

confidence: 99%

Properties of lanK-based regulatory circuit involved in landomycin biosynthesis in Streptomyces cyanogenus S136

Ostash

Zhu

et al. 2010

Russ J Genet

View full text Add to dashboard Cite

show abstract

“…In other cases, the presence of a dedicated PKS initiation module leads to the formation of a non-acetyl derived diketide that is then elongated by the KS-CLF (Hertweck, et al, 2007; Moore and Hertweck, 2002). For example, the initiation module of the doxorubicin ( dps ) PKS (Grimm, et al, 1994) synthesizes a propionyl-CoA derived β-ketopentanoyl-ACP intermediate, whereas the R1128 ( zhu ) initiation module catalyzes formation of a butanoyl-, pentanoyl-, hexanoyl- or 4-methylpentanoyl-ACP thioester (Marti, et al, 2000) (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

In Vivo and In Vitro Analysis of the Hedamycin Polyketide Synthase

Das

Khosla

2009

Chemistry & Biology

View full text Add to dashboard Cite

SUMMARY Hedamycin is an antitumor polyketide antibiotic with unusual biosynthetic features. Earlier sequence analysis of the hedamycin biosynthetic gene cluster implied a role for type I as well as type II polyketide synthases (PKSs). We demonstrate that the hedamycin minimal PKS can synthesize a dodecaketide backbone. The ketosynthase (KS) subunit of this PKS has specificity for both type I and type II acyl carrier proteins (ACPs) with which it collaborates during chain initiation and chain elongation, respectively. The KS receives a C6 primer unit from the terminal ACP domain of HedU (a type I PKS protein) directly, and subsequently interacts with the ACP domain of HedE (a type II PKS protein) during the process of chain elongation. HedE is a bifunctional protein with both ACP and aromatase activity. Its aromatase domain can modulate the chain length specificity of the minimal PKS. Chain length can also be influenced by HedA, the C-9 ketoreductase. Whereas co-expression of the hedamycin minimal PKS and a chain initiation module from the R1128 PKS yields an isobutyryl primed decaketide, the orthologous PKS subunits from the hedamycin gene cluster itself are unable to prime the minimal PKS with a non-acetyl starter unit. Our findings provide new insights into the mechanism of chain initiation and elongation by type II PKSs.

show abstract

“…Identification and characterization of the chd biosynthetic gene cluster (Hertweck et al, 2007). Using a KSa probe (PKSF-PKSR, Table S1; Methods), a genomic fragment containing the putative minimal PKS of the chd gene cluster was cloned, characterized and validated, and used to identify a larger overlapping clone from an A. sulphurea cosmid library which was subsequently sequenced (Methods).…”

Section: Resultsmentioning

confidence: 99%

Identification of the chelocardin biosynthetic gene cluster from Amycolatopsis sulphurea: a platform for producing novel tetracycline antibiotics

et al. 2013

View full text Add to dashboard Cite

Type II Polyketide Synthases: Gaining a Deeper Insight into Enzymatic Teamwork

Abstract: Type II Polyketide Synthases: Gaining a Deeper Insight into Enzymatic Teamwork -[277 refs.]. -(HERTWECK, C.; LUZHETSKYY, A.; REBETS, Y.; BECHTHOLD*, A.; Nat. Prod. Rep. 24 (2007) 1, 162-190; Inst. Pharm., Albert-Ludwigs-Univ., D-79104 Freiburg/Br., Germany; Eng.) -Lindner 23-225

Cited by 64 publications

References 1 publication

Properties of lanK-based regulatory circuit involved in landomycin biosynthesis in Streptomyces cyanogenus S136

Properties of lanK-based regulatory circuit involved in landomycin biosynthesis in Streptomyces cyanogenus S136

In Vivo and In Vitro Analysis of the Hedamycin Polyketide Synthase

Identification of the chelocardin biosynthetic gene cluster from Amycolatopsis sulphurea: a platform for producing novel tetracycline antibiotics

Contact Info

Product

Resources

About