Yunzi Luo

• PhD
• Principal Investigator at Tianjin University

Polycyclic tetramate macrolactams (PTMs) are a widely distributed class of natural products with important biological activities. However, many of these PTMs have not been characterized. Here we apply a plug-and-play synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster SGR810-815 from Streptomyces griseus and discover thre...

As the clustered regularly interspaced short palindromic repeats (CRISPR)–Cas12a (previously known as Cpf1) system cleaves double‐stranded DNA and produces a sticky end, it could serve as a useful tool for DNA assembly/editing. To broaden its application, a variety of engineered FnCas12a proteins are generated with expanded protospacer adjacent mot...

1,3 Glucan synthase (GS) is essential for fungal cell wall biosynthesis. The GS holoenzyme comprises the glycosyltransferase FKS1 and its regulatory factor Rho1, a small GTPase. However, the mechanism by which Rho1 activates FKS1 in a GTP-dependent manner remains unclear. Here, we present two cryo-EM structures of FKS1, apo and in complex with Rho1...

The β-1,3 glucan synthase (GS) is essential for the biosynthesis of β-1,3 glucan, a well-conserved structural component of fungal cell wall. The GS holoenzyme is a multi-enzyme complex consisting of the glycosyltransferase FKS and the essential regulatory factor Rho1, a small GTPase. However, the precise mechanism by which Rho1 activates FKS1 activ...

Natural sugar substitutes are safe, stable, and nearly calorie-free. Thus, they are gradually replacing the traditional high-calorie and artificial sweeteners in the food industry. Currently, the majority of natural sugar substitutes are extracted from plants, which often requires high levels of energy and causes environmental pollution. Recently,...

3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) is a key enzyme in the shikimate pathway for the biosynthesis of aromatic compounds. L-Phe and L-Tyr bind to the two main DAHPS isoforms and inhibit their enzyme activities, respectively. Synthetic biologists aim to relieve such inhibitions in order to improve the productivity of aromatic...

L‐Tyrosine derivatives are widely applied in the pharmaceutical, food, and chemical industries. Their production is mainly confined to chemical synthesis and plant extract. Microorganisms, as cell factories, exhibit promising advantages for valuable chemical production to fulfill the increase in the demand of global markets. Yeast has been used to...

By lacking de novo purine biosynthesis enzymes, Plasmodium falciparum requires purine nucleoside uptake from host cells. The indispensable nucleoside transporter ENT1 of P. falciparum facilitates nucleoside uptake in the asexual blood stage. Specific inhibitors of PfENT1 prevent the proliferation of P. falciparum at submicromolar concentrations. Ho...

Hydroxytyrosol (HT) is a valuable aromatic compound with numerous applications. Herein, we enabled the efficient and scalable de novo HT production in engineered Saccharomyces cerevisiae (S. cerevisiae) from glucose. Starting from a tyrosol-overproducing strain, six HpaB/HpaC combinations were investigated, and the best catalytic performance was ac...

CRISPR-Cas9 from Streptococcus pyogenes has been harnessed as a powerful biotechnological tool for DNA sequence modification. The gRNA binding the recognition lobe (REC lobe) of Cas9 is the initial step of Cas9-mediated DNA cleavage and is a prerequisite to trigger the subsequent conformational transition of Cas9. The functions of REC1-3 domains ha...

While plastics bring convenience to industrial production and daily life, serious environmental problems are always accompanied. Polyurethane is an important polymeric material with versatile applications, but it also accounts for severe plastic contamination worldwide. Since it is difficult for polyurethanes to be completely degraded under natural...

pRS episomal plasmids are widely used in Saccharomyces cerevisiae , owing to their easy genetic manipulations and high plasmid copy numbers (PCNs). Nevertheless, their broader application is hampered by the instability of the pRS plasmids. In this study, we designed an episomal plasmid based on the endogenous 2μ plasmid with both improved stability...

Poly(ethylene terephthalate) (PET) is one of the most widely used synthetic polyesters, but also a major cause of plastic pollution. Because the chemical degradation of PET would be uneconomical and rather burdensome, considerable efforts have been devoted to exploring enzymatic processes for the disposal of PET waste. Many PET‐hydrolyzing enzymes...

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical...

Daptomycin (DAP) is a novel microbial lipopeptide antibiotic synthesized by the DAP biosynthetic gene cluster dpt of Streptomyces roseosporus (S. roseosporus). DptP gene locates upstream of dpt and confers DAP resistance to Streptomyces ambofaciens (S. ambofaciens). So far, the biological functions of dptP gene for S. roseosporus growth are still c...

Glycosylation possess prominent biological and pharmacological significance in natural product and drug candidate synthesis. The glycosyltransferase YjiC, discovered from Bacillus subtilis (Bs-YjiC), shows potential applications in drug development due to its wide substrate spectrums. In order to elucidate its catalytic mechanism, we solved the cry...

Tyrosol and its glycosylated product salidroside are important ingredients in pharmaceuticals, nutraceuticals and cosmetics. Despite the ability of Saccharomyces cerevisiae to naturally synthesize tyrosol, high yield from de novo synthesis remains a challenge. Here, we used metabolic engineering strategies to construct S. cerevisiae strains for hig...

Streptomyces strains produce a great number of valuable natural products. With the development of genome sequencing, a vast number of biosynthetic gene clusters with high potential for use in the discovery of valuable clinical drugs have been revealed. Therefore, emerging needs for tools to manipulate these biosynthetic pathways are presented. Alth...

Streptomyces is an important treasure trove for natural products discovery. In recent years, many scientists focused on the genetic modification and metabolic regulation of Streptomyces to obtain diverse bioactive compounds with high yields. This review summarized the commonly used regulatory strategies for natural products discovery and overproduc...

Intestinal bacteria interact closely with human health and diseases. With the development of high-throughput sequencing technologies, researchers have discovered the potential of intestinal bacteria in the diagnosis and treatment of diseases. Meanwhile, synthetic biology strategies are applied to engineer these bacteria for clinical applications. T...

Natural products of microbial origin have proven to be the wellspring of clinically useful compounds for human therapeutics. Streptomyces species are predominant sources of bioactive compounds, most of which serve as potential drug candidates. While the exploitation of natural products has been severely reduced over the past two decades, the growin...

Since 2013, the CRISPR-based bacterial antiviral defense systems have revolutionized the genome editing field. In addition to genome editing, CRISPR has been developed as a variety of tools for gene expression regulations, live cell chromatin imaging, base editing, epigenome editing, and nucleic acid detection. Moreover, in the context of further b...

Measuring the absolute protein expression quantity for a specific promoter is necessary in the fields of both molecular biology and synthetic biology. The strength of a promoter is traditionally characterized by measuring the fluorescent intensity of the fluorescent protein downstream of the promoter. Until now, measurement of the absolute protein...

The cover feature picture shows that PETase, a newly discovered enzyme from Ideonella sakaiensis, has high efficiency and specificity towards PET plastics compared to other similar enzymes (such as cutinase, esterase, or lipase). We have analyzed its crystal structure and improved its catalytic efficiency through site mutagenesis. The results sugge...

Compared with traditional recycle strategies, biodegradation provides a sustainable solution for poly (ethylene terephthalate) (PET) wastes disposal. PETase, a newly identified enzyme from Ideonella sakaiensis, has high efficiency and specificity towards PET, which provides a prominent prospect on PET degradation. Based on the biochemical analysis,...

Covering: 2010 to 2015Natural product scaffolds remain a major source and inspiration for human therapeutics. However, generation of a natural product in the post-genomic era often requires reconstruction of the corresponding biosynthetic gene cluster in a heterologous host. In the burgeoning fields of synthetic biology and metabolic engineering, a...

Natural products produced by microorganisms and plants are a major resource of antibacterial and anticancer drugs as well as industrially useful compounds. However, the native producers often suffer from low productivity and titers. Here we summarize the recent applications of heterologous biosynthesis for the production of several important classe...

Actinomycetes are important organisms for biosynthesis of valuable natural products. However, only a limited number of well-characterized native constitutive promoters from actinomycetes are available for the construction and engineering of large biochemical pathways. Here we report the discovery and characterization of 32 candidate promoters ident...

A fundamental challenge in basic and applied biology is to reprogram cells with improved or novel traits on a genomic scale. However, the current ability to reprogram a cell on the genome scale is limited to bacterial cells. Here we report RNA interference (RNAi)-assisted genome evolution (RAGE) as a generally applicable method for genome-scale eng...

Microbial production of higher alcohols from renewable feedstock has attracted intensive attention thanks to its potential as a source for next-generation gasoline substitutes. Here we report the discovery, characterization and engineering of an endogenous 1-butanol pathway in Saccharomyces cerevisiae. Upon introduction of a single gene deletion ad...

With its expanding toolkit of sophisticated computational and experimental techniques, synthetic biology is currently poised to be a significant contributor to the discovery and development of the next generation of drugs derived from natural products. In this chapter, a number of tools are highlighted which enable the identification, analysis, ass...

Natural products (secondary metabolites) are a rich source of compounds with important biological activities. Eliciting pathway expression is always challenging but extremely important in natural product discovery because an individual pathway is tightly controlled through a unique regulation mechanism and hence often remains silent under the routi...

The increasing availability of whole genome sequences has revised our view of the metabolic capabilities of microorganisms. Analyses of more than 500 microbial genome sequences currently in the publicly-accessible databases have revealed numerous examples of gene clusters encoding enzymes similar to those known to be involved in the biosynthesis of...

DNA assembler enables design and rapid construction of biochemical pathways in a one-step fashion by exploitation of the in vivo homologous recombination mechanism in Saccharomyces cerevisiae. It has many applications in pathway engineering, metabolic engineering, combinatorial biology, and synthetic biology. Here we use the zeaxanthin biosynthetic...

Computational analysis of sequenced genomes and metagenomes has revealed numerous gene clusters that are potentially involved in the biosynthesis of natural products. However, many of these gene clusters produce unknown products. Hence they are called cryptic biosynthetic pathways. We recently developed a highly efficient one-step method, so-called...

Type III polyketide synthases (PKSs) are the condensing enzymes that catalyze the formation of a myriad of aromatic polyketides in plant, bacteria, and fungi. Here we report the cloning and characterization of a putative type III PKS from Aspergillusniger, AnPKS. This enzyme catalyzes the synthesis of alkyl pyrones from C2 to C18 starter CoA thioes...

We report a synthetic biology strategy for rapid genetic manipulation of natural product biosynthetic pathways. Based on DNA assembler, this method synthesizes the entire expression vector containing the target biosynthetic pathway and the genetic elements required for DNA maintenance and replication in various hosts in a single-step manner through...

The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, a...

Eucalyptus species synthesize a wealth of polyketide natural products, but no relevant biosynthetic enzyme has been identified. Degenerate primers designed from conserved regions of fourteen chalcone synthase superfamily enzymes were used to isolate gene fragments from at least five different Type III polyketide synthases (PKSs) in E. camaldulensis...

The assembly of large recombinant DNA encoding a whole gene cluster represents a significant challenge in metabolic engineering and synthetic biology. We recently developed DNA assembler, a highly efficient one-step method for rapid construction of a multi-gene biochemical pathway via in vivo homologous recombination in Saccharomyces cerevisiae. He...