Showing papers by "F. Hahn published in 2022"

Studying a Bottleneck of Multimodular Polyketide Synthase Processing: the Polyketide Structure-Dependent Performance of Ketoreductase Domains.

Abstract: Ketoreductases (KRs) are canonical domains of type I polyketide synthases (PKSs). They stereoselectively reduce ACP-bound β-ketothioester intermediates and are responsible for a large part of the stereocenters in reduced polyketides. Albeit essential for the understanding and engineering of PKS, the specific effects of altering the polyketide part of KR precursors on their performance has rarely been studied. We present investigations on the substrate-dependent performance of six isolated KR domains using a library of structurally diverse surrogates for PKS thioester intermediates. A pronounced correlation between the polyketide structure and the KR performance was observed with activity and stereoselectivity diminishing with growing deviation from the natural KR precursor structure. The extent of this decrease and the profile of arising side products was characteristic for the individual KRs. Our results reinforce the importance of structure-KR performance relationships and suggest extended studies with isolated domains and whole PKS modules.

Towards understanding oxygen heterocycle-forming biocatalysts: a selectivity study of the pyran synthase PedPS7.

Abstract: Intramolecular oxa-Michael addition-catalysing cyclases are widespread in polyketide biosynthetic pathways. Although they have significant potential in biotechnology and chemoenzymatic synthesis of chiral heterocycles, they have only scarcely been studied. Here, we present detailed investigations on the selectivity profile of the pyran synthase PedPS7 showing that it combines broad substrate tolerance with high selectivity for the formation of up to two new stereocentres and relaxed precursor stereoisomer discrimination. Two of the four possible tetrahydropyran stereoisomers are reliably accessible by this enzyme. The results indicate fundamental differences between the individual subtypes of intramolecular oxa-Michael addition-catalysing cyclases.

Measurement of the very rare K+→π+νν¯ decay at the NA62 experiment

Abstract: The K+→π+νν¯ decay, with a very precisely predicted branching ratio of less than 10−10, is among the best processes to reveal indirect effects of new physics. The NA62 experiment reports the branching ratio measurement BR( K+→π+νν¯ ) = 1.06−0.34+0.40|stat ± 0.009| syst ) · 10−10 at 68% CL, based on the observation of 20 signal candidates with an expected background of 7.0 events from the total data sample collected at the CERN SPS during 2016-2018. This provides evidence for the very rare K+→π+νν¯ decay, observed with a significance of 3.4σ. This measurement is also used to set limits on BR(K + → π +X), where X is a new feebly interacting scalar or pseudo-scalar particle, foreseen in several new physics scenarios.

Search for K+ decays to a lepton and invisible particles

Abstract: The NA62 experiment at CERN reports searches for K + → e + N , K + → µ + N and K + → µ + X decays, where N and X are massive invisible particles, using the 2016-2018 data set. The N particle is assumed to be a heavy neutral lepton, and the results are expressed as upper limits of O ( 10 − 9 ) and O ( 10 − 8 ) on the neutrino mixing parameter | U e 4 | 2 and | U µ 4 | 2 , improving on the earlier searches for heavy neutral lepton production and decays in the kinematically accessible mass range. The X particle is considered a scalar or vector hidden sector mediator decaying to an invisible final state, and upper limits of the decay branching fraction for X masses in the range 10-370 MeV/c 2 are reported for the first time, ranging from O ( 10 − 5 ) to O ( 10 − 7 ) . An upper limit of 1 . 0 · 10 − 6 is established at 90% CL on the K + → µ + νν ¯ ν branching fraction.