Nonlinearity in Bacterial Population Dynamics: Proposal for Experiments for the Observation of Abrupt Transitions in Patches

An explicit proposal for experiments leading to abrupt transitions in spatially extended bacterial populations in a Petri dish is presented on the basis of an exact formula obtained through an analytic theory. The theory provides accurately the transition expressions in spite of the fact that the actual solutions, which involve strong nonlinearity, are inaccessible to it. The analytic expressions are verified through numerical solutions of the relevant nonlinear equation. The experimental set-up suggested uses opaque masks in a Petri dish bathed in ultraviolet radiation as in Lin et al., Biophys. J. {\bf 87}, 75 (2004) and Perry, J. R. Soc. Interface {\bf 2}, 379 (2005) but is based on the interplay of two distances the bacteria must traverse, one of them favorable and the other adverse. As a result of this interplay feature, the experiments proposed introduce highly enhanced reliability in interpretation of observations and in the potential for extraction of system parameters.Comment: 5 figure

Evidence for enzyme catalysed intramolecular [4+2] Diels-Alder cyclization during the biosynthesis of pyrichalasin H

Cytochalasans are highly complex fungal metabolites which exhibit diverse biological activities. Little is known of the chemical steps involved in the construction of the tricyclic core, which consists of an octahydro-isoindole skeleton fused to a macrocyclic ring. Here, using a directed gene knockout and complementation strategy, we show that PyiF is implicated as the proposed intramolecular [4+2] Diels-Alderase required for construction of the tricyclic core of pyrichalasin H 1. © 2020 The Royal Society of Chemistry

Engineering Aspergillus oryzae for the Heterologous Expression of a Bacterial Modular Polyketide Synthase

Microbial natural products have had phenomenal success in drug discovery and development yet form distinct classes based on the origin of their native producer. Methods that enable metabolic engineers to combine the most useful features of the different classes of natural products may lead to molecules with enhanced biological activities. In this study, we modified the metabolism of the fungus Aspergillus oryzae to enable the synthesis of triketide lactone (TKL), the product of the modular polyketide synthase DEBS1-TE engineered from bacteria. We established (2S)-methylmalonyl-CoA biosynthesis via introducing a propionyl-CoA carboxylase complex (PCC); reassembled the 11.2 kb DEBS1-TE coding region from synthetic codon-optimized gene fragments using yeast recombination; introduced bacterial phosphopantetheinyltransferase SePptII; investigated propionyl-CoA synthesis and degradation pathways; and developed improved delivery of exogenous propionate. Depending on the conditions used titers of TKL ranged from <0.01–7.4 mg/L. In conclusion, we have demonstrated that A. oryzae can be used as an alternative host for the synthesis of polyketides from bacteria, even those that require toxic or non-native substrates. Our metabolically engineered A. oryzae may offer advantages over current heterologous platforms for producing valuable and complex natural products

Heterologous Expression of Secondary Metabolite Genes in Trichoderma reesei for Waste Valorization

Trichoderma reesei (Hypocrea jecorina) was developed as a microbial cell factory for the heterologous expression of fungal secondary metabolites. This was achieved by inactivation of sorbicillinoid biosynthesis and construction of vectors for the rapid cloning and expression of heterologous fungal biosynthetic genes. Two types of megasynth(et)ases were used to test the strain and vectors, namely a non-reducing polyketide synthase (nr-PKS, aspks1) from Acremonium strictum and a hybrid highly-reducing PKS non-ribosomal peptide synthetase (hr-PKS-NRPS, tenS + tenC) from Beauveria bassiana. The resulting engineered T. reesei strains were able to produce the expected natural products 3-methylorcinaldehyde and pretenellin A on waste materials including potato, orange, banana and kiwi peels and barley straw. Developing T. reesei as a heterologous host for secondary metabolite production represents a new method for waste valorization by the direct conversion of waste biomass into secondary metabolites

Biosynthesis of 6-Hydroxymellein Requires a Collaborating Polyketide Synthase-like Enzyme

The polyketide synthase (PKS)-like protein TerB, consisting of inactive dehydratase, inactive C-methyltransferase, and functional ketoreductase domains collaborates with the iterative non reducing PKS TerA to produce 6-hydroxymellein, a key pathway intermediate during the biosynthesis of various fungal natural products. The catalytically inactive dehydratase domain of TerB appears to mediate productive interactions with TerA, demonstrating a new mode of trans-interaction between iterative PKS components

Particle Statistics and Population Dynamics

We study a master equation system modelling a population dynamics problem in a lattice. The problem is the calculation of the minimum size of a refuge that can protect a population from hostile external conditions, the so called critical patch size problem. We analize both cases in which the particles are considered fermions and bosons and show using exact analitical methods that, while the Fermi-Dirac statistics leads to certain extinction for any refuge size, the Bose-Eistein statistics allows survival even for the minimal refuge

Diels–Alder Reactions During the Biosynthesis of Sorbicillinoids

The sorbicillinoids are a class of biologically active and structurally diverse fungal polyketides arising from sorbicillin. Through co-expression of sorA, sorB, sorC, and sorD from Trichoderma reesei QM6a, the biosynthetic pathway to epoxysorbicillinol and dimeric sorbicillinoids, which resemble Diels–Alder-like and Michael-addition-like products, was reconstituted in Aspergillus oryzae NSAR1. Expression and feeding experiments demonstrated the crucial requirement of the flavin-dependent monooxygenase SorD for the formation of dimeric sorbicillinoids, hybrid sorbicillinoids, and epoxysorbicillinol in vivo. In contrast to prior reports, SorD catalyses neither the oxidation of 2',3'-dihydrosorbicillin to sorbicillin nor the oxidation of sorbicillinol to oxosorbicillinol. This is the first report that both the intermolecular Diels–Alder and Michael dimerization reactions, as well as the epoxidation of sorbicillinol are catalysed in vivo by SorD. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA

Periodically Varying Externally Imposed Environmental Effects on Population Dynamics

Effects of externally imposed periodic changes in the environment on population dynamics are studied with the help of a simple model. The environmental changes are represented by the temporal and spatial dependence of the competition terms in a standard equation of evolution. Possible applications of the analysis are on the one hand to bacteria in Petri dishes and on the other to rodents in the context of the spread of the Hantavirus epidemic. The analysis shows that spatio-temporal structures emerge, with interesting features which depend on the interplay of separately controllable aspects of the externally imposed environmental changes.Comment: 7 pages, 8 figures, include