摘要：In the recent years,engineering new-to-nature CO_(2)-and C1-fixing metabolic pathways made a leap ***,artificial pathways promise higher yields and activity than natural ones like the Calvin-Benson-Bassham(CBB)*** question remains how to best predict their in vivo performance and what actually makes one pathway“better”than *** this context,we explore aerobic carbon fixation pathways by a computational approach and compare them based on their specific activity and yield on methanol,formate,and CO_(2)/H_(2)considering the kinetics and thermodynamics of the *** pathways found in nature or implemented in the laboratory,this included two completely new cycles with favorable features:the reductive citramalyl-CoA cycle and the 2-hydroxyglutarate-reverse tricarboxylic acid cycle.A comprehensive kinetic data set was collected for all enzymes of all pathways,and missing kinetic data were sampled with the Parameter Balancing *** and thermodynamic data were fed to the Enzyme Cost Minimization algorithm to check for respective inconsistencies and calculate pathway-specific *** specific activities of the reductive glycine pathway,the CETCH cycle,and the new reductive citramalyl-CoA cycle were predicted to match the best natural cycles with superior productsubstrate ***,the CBB cycle performed better in terms of activity compared to the alternative pathways than previously *** make an argument that stoichiometric yield is likely not the most important design criterion of the CBB ***,alternative carbon fixation pathways were paretooptimal for specific activity and product-substrate yield in simulations with C1 substrates and CO_(2)/H_(2)and therefore hold great potential for future applications in Industrial biotechnology and Synthetic Biology.

摘要：Phloretin is an important skin-lightening and depigmenting agent from the peel of apples. Although de novo production of phloretin has been realized in microbes using the natural pathway from plants, the efficiency of phloretin production is still not enough for industrial application. Here, we established an artificial pathway in the yeast to produce phloretin via assembling two genes of p-coumaroyl-CoA ligase(4CL) and chalcone synthase(CHS). CHS is a key enzyme which conventionally condenses a CoA-tethered starter with three molecules of malonyl-CoA to form the backbone of flavonoids. However, there was 33% of byproduct generated via CHS by condensing two molecules of malonyl-CoA during the fermentation process. Hence, we introduced a more efficient CHS and improved the supply of malonyl-CoA through two pathways;the by-product ratio was decreased from 33% to 17% and the production of phloretin was improved from 48 to 83.2 mg L^(-1). Finally, a fed-batch fermentation process was optimized and the production of phloretin reached 619.5 mg L^(-1), which was 14-fold higher than that of the previous studies. Our work established a platform for the biosynthesis of phloretin from the low-cost raw material 3-(4-hydroxyphenyl) propanoic acid and also illustrated the potential for industrial scale bio-manufacturing of phloretin.

摘要：In the article titled“In-Depth Computational Analysis of Natural and Artificial Carbon Fixation Pathways”[1],there were errors in Figures 7–*** the label of Figure 9,it reads:“Glyceraldehyde-3-phosphate was chosen as a product for the pathways,”but this is corrected to“Pyruvate was chosen as a product and formate as a substrate for the pathways.”In the lower panels of Figures 7,8,and 10,the labels“MOG/rCCC”and“CETCH cycle”in the figure key should be ***,in these figures,the panel indicators(a)and(b)were missing.

摘要：Revolutionary breakthroughs in artificial intelligence (AI) and machine learning (ML) have had a profound impact on a widerange of scientific disciplines, including the development of artificial cell factories for biomanufacturing. In this paper, wereview the latest studies on the application of data-driven methods for the design of new proteins, pathways, and strains. Wefirst briefly introduce the various types of data and databases relevant to industrial biomanufacturing, which are the basis fordata-driven research. Different types of algorithms, including traditional ML and more recent deep learning methods, are alsopresented. We then demonstrate how these data-based approaches can be applied to address various issues in cell factorydevelopment using examples from recent studies, including the prediction of protein function, improvement of metabolicmodels, and estimation of missing kinetic parameters, design of non-natural biosynthesis pathways, and pathway *** the last section, we discuss the current limitations of these data-driven approaches and propose that data-driven methodsshould be integrated with mechanistic models to complement each other and facilitate the development of synthetic strains forindustrial biomanufacturing.

摘要：Functional manipulation of biosynthetic enzymes such as cytochrome P450 s(or P450 s) has attracted great interest in metabolic engineering of plant natural *** and mogrosides are plant triterpenoids that share the same backbone but display contrasting *** structural and functional diversity of the two metabolites can be manipulated by engineering P450 ***,the functional redesign of P450 s through directed evolution(DE) or structure-guided protein engineering is time consuming and challenging,often because of a lack of high-throughput screening methods and crystal structures of P450 *** this study,we used an integrated approach combining computational protein design,evolutionary information,and experimental data-driven optimization to alter the substrate specificity of a multifunctional P450(CYP87 D20)from *** three rounds of iterative design and evaluation of 96 protein variants,CYP87 D20,which is involved in the cucurbitacin C biosynthetic pathway,was successfully transformed into a P450 mono-oxygenase that performs a single specific hydroxylation at C11 of *** integrated P450-engineering approach can be further applied to create a de novo pathway to produce mogrol,the precursor of the natural sweetener mogroside,or to alter the structural diversity of plant triterpenoids by functionally manipulating other P450 s.

摘要：Vectored non-covalent interactions—mainly hydrogen bonding and aromatic interactions—extensively contribute to(bio)-organic self-assembling processes and significantly impact the physicochemical properties of the associated ***,vectored non-covalent interaction-driven assembly occursmainly along one-dimensional(1D)or three-dimensional(3D)directions,and a two-dimensional(2D)orientation,especially that of multilayered,graphene-like assembly,has been reported *** this present research,by introducing amino,hydroxyl,and phenyl moieties to the triazine skeleton,supramolecular layered assembly is achieved by vectored non-covalent *** planar hydrogen bonding network results in high stability,with a thermal sustainability of up to about 330°C and a Young’s modulus of up to about 40 *** introducing wrinkles by biased hydrogen bonding or aromatic interactions to disturb the planar organization,the stability ***,the intertwined aromatic interactions prompt a red edge excitation shift effect inside the assemblies,inducing broad-spectrum fluorescence covering nearly the entire visible light region(400–650 nm).We show that bionic,superhydrophobic,pillar-like arrays with contact angles of up to about 170°can be engineered by aromatic interactions using a physical vapor deposition approach,which cannot be realized through hydrogen *** findings show the feasibility of 2D assembly with engineerable properties by modulating vectored non-covalent interactions.

摘要：Plant-based bioproduction of insect sex pheromones has been proposed as an innovative strategy to increase the sustainability of pest control in ***,we describe the engineering of transgenic plants producing(Z)-11-hexadecenol(Z11-16OH)and(Z)-11-hexadecenyl acetate(Z11-16OAc),two main volatile components in many Lepidoptera sex pheromone *** assembled multigene DNA constructs encoding the pheromone biosynthetic pathway and stably transformed them into Nicotiana benthamiana *** constructs contained the Amyelois transitella AtrΔ11 desaturase gene,the Helicoverpa armigera fatty acyl reductase HarFAR gene,and the Euonymus alatus diacylglycerol acetyltransferase EaDAct gene in different *** the pheromone-producing plants showed dwarf phenotypes,the severity of which correlated with pheromone *** but one of the recovered lines produced high levels of Z11-16OH,but very low levels of Z11-16OAc,probably as a result of recurrent truncations at the level of the EaDAct *** one plant line(SxPv1.2)was recovered that harboured an intact pheromone pathway and which produced moderate levels of Z11-16OAc(11.8μg g^(-1) FW)and high levels of Z11-16OH(111.4μg g^(-1)).Z11-16OAc production was accompanied in SxPv1.2 by a partial recovery of the dwarf ***1.2 was used to estimate the rates of volatile pheromone release,which resulted in 8.48 ng g-1 FW per day for Z11-16OH and 9.44 ng g^(-1 )FW per day for *** results suggest that pheromone release acts as a limiting factor in pheromone biodispenser strategies and establish a roadmap for biotechnological improvements.

摘要：Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical *** has also been employed in various advanced industrial *** development of intelligent biomedical engineering has raised the requirements for 3D printing,such as flexible manufacturing processes and technologies,biocompatible constituents,and alternative ***,state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields,thus severely limiting applications demanding biocompatibility and *** this regard,peptide architectonics,which are self-assembled by programmed amino acid sequences that can be flexibly functionalized,have shown promising potential as bioinspired inks for 3D ***,the combination of 3D printing and peptide self-assembly poten-tially opens up an alternative avenue of 3D bioprinting for diverse advanced ***,a small but innovative nation,has significantly contributed to 3D bioprinting in terms of scientific studies,marketization,and peptide architectonics,including modulations and applications,and ranks as a leading area in the 3D bioprinting *** review summarizes the recent progress in 3D bioprinting in Israel,focusing on scientific studies on printable components,soft devices,and tissue *** paper further delves into the manufacture of industrial products,such as artificial meats and bioinspired supramolecular architectures,and the mechanisms,physicochemical properties,and applications of peptide ***,Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.

摘要：Human life intimately depends on plants for food,biomaterials,health,energy,and a sustainable *** plants have been genetically improved mostly through breeding,along with limited modification via genetic engineering,yet they are still not able to meet the ever-increasing needs,in terms of both quantity and quality,resulting from the rapid increase in world population and expected standards of living.A step change that may address these challenges would be to expand the potential of plants using biosystems design *** represents a shift in plant science research from relatively simple trial-and-error approaches to innovative strategies based on predictive models of biological *** biosystems design seeks to accelerate plant genetic improvement using genome editing and genetic circuit engineering or create novel plant systems through de novo synthesis of plant *** this perspective,we present a comprehensive roadmap of plant biosystems design covering theories,principles,and technical methods,along with potential applications in basic and applied plant biology *** highlight current challenges,future opportunities,and research priorities,along with a framework for international collaboration,towards rapid advancement of this emerging interdisciplinary area of ***,we discuss the importance of social responsibility in utilizing plant biosystems design and suggest strategies for improving public perception,trust,and acceptance.