Conformal field theory-data analysis for N=4\mathcal{N} = 4 Super-Yang-Mills at strong coupling

We analyse the CFT-data of planar 4D $\mathcal{N} = 4$ Super-Yang-Mills theory at strong coupling. By combining spectral data extracted from integrability, with recent advances in computing the AdS Virasoro-Shapiro amplitude, we extract predictions for leading order OPE coefficients on entire Kaluza-Klein (KK-)towers of states. We observe that the leading order OPE coefficients for all states in a given KK-tower are the same. Furthermore, we also notice that, in many cases, the leading order OPE coefficients of all states in the KK-tower vanish, suggesting a simplification of the physics in this limit.Comment: 17 pages, 3 table

Striving for sustainable biosynthesis:discovery, diversification, and production of antimicrobial drugs in<i> Escherichia coli</i>

New antimicrobials need to be discovered to fight the advance of multidrug-resistant pathogens. A promising approach is the screening for antimicrobial agents naturally produced by living organisms. As an alternative to studying the native producer, it is possible to use genetically tractable microbes as heterologous hosts to aid the discovery process, facilitate product diversification through genetic engineering, and ultimately enable environmentally friendly production. In this mini-review, we summarize the literature from 2017 to 2022 on the application of Escherichia coli and E. coli-based platforms as versatile and powerful systems for the discovery, characterization, and sustainable production of antimicrobials. We highlight recent developments in high-throughput screening methods and genetic engineering approaches that build on the strengths of E. coli as an expression host and that led to the production of antimicrobial compounds. In the last section, we briefly discuss new techniques that have not been applied to discover or engineer antimicrobials yet, but that may be useful for this application in the future

Fast QSC Solver: tool for systematic study of N=4 Super-Yang-Mills spectrum

Integrability methods give us access to a number of observables in the planar N=4 SYM. Among them, the Quantum Spectral Curve (QSC) governs the spectrum of anomalous dimensions. Low lying states were successfully studied in the past using the QSC. However, with the increased demand for a systematic study of a large number of states for various applications, there is a clear need for a fast QSC solver which can easily access a large number of excited states. Here, we fill this gap by developing a new algorithm and applied it to study all 219 states with the bare dimension Δ0≤6 in a wide range of couplings. The new algorithm has an improved performance at weak coupling and allows to glue numerics smoothly the available perturbative data, resolving the previous obstruction. Further ~ 8-fold efficiency gain comes from C++ implementation over the best available Mathematica implementation. We have made the code and the data to be available via a GitHub repository. The method is generalisable for non-local observables as well as for other theories such as deformations of N=4 SYM and ABJM. It may find applications in the separation of variables and bootstrability approaches to the correlation functions. Some applications to correlators at strong coupling are also presented

Exact summation of leading infrared logarithms in 2D effective field theories

A method of exact all-order summation of leading infrared logarithms in two dimensional massless $\Phi^4$-type non-renormalizable effective field theories (EFTs) is developed. The method is applied to the ${\rm O}(N)$-symmetric EFT, which is a two-dimensional sibling of the four dimensional ${\rm O}(N+1)/{\rm O}(N)$ sigma-model. For the first time the exact all-order summation of the $\left(E^{2} \ln(1/E)\right)^n$ contributions (chiral logarithms) for the $2 \to 2$ scattering amplitudes is performed in closed analytical form. The cases when the resulting amplitudes turn to be meromorphic functions with an infinite number of poles (Landau poles) are identified. This provides the first explicit example of quasi-renormalizable field theories.Comment: 22 pages, 2 figure

Structural characterization and extended substrate scope analysis of two Mg&lt;sup&gt;2+&lt;/sup&gt;-dependent O-methyltransferases from bacteria

Oxygen-directed methylation is a ubiquitous tailoring reaction in natural product pathways catalysed by O-methyltransferases (OMTs). Promiscuous OMT biocatalysts are thus a valuable asset in the toolkit for sustainable synthesis and optimization of known bioactive scaffolds for drug development. Here, we characterized two bacterial OMTs from Desulforomonas acetoxidans and Streptomyces avermitilis in terms of their enzymatic properties and substrate scope and determined their crystal structures. Both OMTs methylated a wide range of catechol-like substrates, including flavonoids, coumarins, hydroxybenzoic acids and their respective aldehydes, an anthraquinone and an indole. One enzyme also accepted a steroid. The product range included pharmaceutically relevant compounds such as (iso)fraxidin, iso(scopoletin), chrysoeriol, alizarin 1-methyl ether and 2-methoxyestradiol. Interestingly, certain non-catechol flavonoids and hydroxybenzoic acids were also methylated. This study expands the knowledge on substrate preference and structural diversity of bacterial catechol OMTs and paves the way for their use in (combinatorial) pathway engineering.Table of contents Two promiscuous O-methyltransferases from bacteria were found to methylate a panel of catechol substrates towards high-value medicinal compounds. Surprisingly, the non-catechol substrates 5-hydroxyflavonoids and o-hydroxybenzoic acids/aldehydes were also methylated at low conversion rates. The crystal structures reveal potential target sites for enzyme engineering for biocatalytic applications.Competing Interest StatementThe authors have declared no competing interest

Structural Characterization and Extended Substrate Scope Analysis of Two Mg²⁺-Dependent O-Methyltransferases from Bacteria**

Oxygen-directed methylation is a ubiquitous tailoring reaction in natural product pathways catalysed by O-methyltransferases (OMTs). Promiscuous OMT biocatalysts are thus a valuable asset in the toolkit for sustainable synthesis and optimization of known bioactive scaffolds for drug development. Here, we characterized the enzymatic properties and substrate scope of two bacterial OMTs from Desulforomonas acetoxidans and Streptomyces avermitilis and determined their crystal structures. Both OMTs methylated a wide range of catechol-like substrates, including flavonoids, coumarins, hydroxybenzoic acids, and their respective aldehydes, an anthraquinone and an indole. One enzyme also accepted a steroid. The product range included pharmaceutically relevant compounds such as (iso)fraxidin, iso(scopoletin), chrysoeriol, alizarin 1-methyl ether, and 2-methoxyestradiol. Interestingly, certain non-catechol flavonoids and hydroxybenzoic acids were also methylated. This study expands the knowledge on substrate preference and structural diversity of bacterial catechol OMTs and paves the way for their use in (combinatorial) pathway engineering.</p

MIBiG 3.0 : a community-driven effort to annotate experimentally validated biosynthetic gene clusters

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/

Striving for sustainable biosynthesis: discovery, diversification, and production of antimicrobial drugs in Escherichia coli

New antimicrobials need to be discovered to fight the advance of multidrug-resistant pathogens. A promising approach is the screening for antimicrobial agents naturally produced by living organisms. As an alternative to studying the native producer, it is possible to use genetically tractable microbes as heterologous hosts to aid the discovery process, facilitate product diversification through genetic engineering, and ultimately enable environmentally friendly production. In this mini-review, we summarize the literature from 2017 to 2022 on the application of Escherichia coli and E. coli-based platforms as versatile and powerful systems for the discovery, characterization, and sustainable production of antimicrobials. We highlight recent developments in high-throughput screening methods and genetic engineering approaches that build on the strengths of E. coli as an expression host and that led to the production of antimicrobial compounds. In the last section, we briefly discuss new techniques that have not been applied to discover or engineer antimicrobials yet, but that may be useful for this application in the future