About

Ziqiang Guan is a Research Professor in the Department of Biochemistry at Duke University. His primary affiliation is with the Guan Lab, where he contributes to research in biochemistry. His contact email is zguan@biochem.duke.edu. The department is located at 240 Nanaline H Duke, Durham, NC 27710, with a mailing address at Duke Box 3711, Durham, NC 27710. Further details about his research focus, background, and key contributions are not provided on the page.

Research topics

• Biology
• Biochemistry
• Cell biology
• Chemistry

Selected publications

• CpgD is a phosphoglycerate cytidylyltransferase required for ceramide diphosphoglycerate synthesis

  Journal of Biological Chemistry · 2025-06-16 · 2 citations

  articleOpen access

  LPS is essential in most Gram-negative bacteria, but mutants of several species have been isolated that can survive in its absence. Caulobacter crescentus viability in the absence of LPS is partially dependent on the anionic sphingolipid ceramide diphosphoglycerate (CPG2). Genetic analyses showed that ccna_01210, which encodes a nucleotidyltransferase, is required for CPG2 production. Using purified recombinant protein, we determined that CCNA_01210 (CpgD) is a phosphoglycerate cytidylyltransferase that uses CTP and phosphoglycerate to produce CDP-glycerate, which we hypothesize is the phosphoglycerate donor for CPG2 synthesis. CpgD had optimum activity at pH 7.5 to 8 in the presence of magnesium. CpgD exhibited Michaelis-Menten kinetics concerning 3-phosphoglycerate, D-2-phosphoglycerate, and L-2-phosphoglycerate. By contrast, CTP followed Michaelis-Menten kinetics in the presence of 3-phosphoglycerate and L-2-phosphoglycerate but exhibited cooperativity with D-2-phosphoglycerate. Overall, D-2-phosphoglycerate was the preferred substrate in vitro. The characterization of this enzyme uncovers another step in the pathway toward CPG2 synthesis.

  PublisherOA PDFDOI

• A biosynthetic pathway for ornithine lipid formation dependent on a GH3 (Gretchen Hagen 3)-like enzyme in planctomycetes

  Journal of Biological Chemistry · 2025-08-27 · 5 citations

  articleOpen access

  as cofactor. A phylogenomic analysis showed that bacterial GH3-homologues are widely distributed across diverse bacterial phyla. We conclude that bacterial GH3-like enzymes, such as OlsH described here, catalyze the initial step in OL synthesis in the planctomycete S. acidiphila and likely in other bacteria as well. These findings expand our understanding of bacterial lipid diversity and suggest evolutionary convergence in OL biosynthesis.

  PublisherOA PDFDOI

• Characterization of age-related dolichol increases in the retina of the C57BL/6 mouse

  Scientific Reports · 2025-12-29

  articleOpen access

  Dolichol is a lipid uniquely important for retinal cells. Mutations affecting dolichol biosynthesis cause non-syndromic retinal degeneration. Aging is a major risk factor for leading causes of vision loss. We characterized age-related changes in dolichol levels in the retinas of C57BL/6 mice of both sexes at the age of PD (postnatal day) 5, 10, 15, 20, 30, 60, 180, 360, and 600 using liquid chromatography-mass spectrometry (LC-MS), a highly sensitive and specific method for dolichol analysis. All four major dolichol species-dolichol-17 (Dol-17), Dol-18, Dol-19, and Dol-20, increased dramatically with age. The largest increase was in Dol-18, which rose by a factor of 100 from PD 5 to PD 600. Age-related dolichol increases occurred in two distinct phases: Phase I (PD 5 to PD 30) and Phase II (PD 30 to PD 600). These phases coincide with the phases of postnatal development and adult aging, respectively. A shift in the dolichol chain-length profile with age was also observed. Dol-19 was the dominant species from PD 5 to PD 15 but Dol-18 became dominant after PD 20. Changes in cholesterol and coenzyme Q9 (CoQ9) followed the same biphasic pattern. The age-related increase in dolichol levels may influence the physical properties of cell membranes, act as an ultraviolet (UV) filter for retinal cells, and serve as a biomarker of retinal aging.

  PublisherDOI

• BPS2025 - Coevolutionary motifs enable discovery of novel lipid specificity in multiple peptide resistance factor enzyme

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

• Structure and inhibition mechanisms of Mycobacterium tuberculosis essential transporter efflux protein A

  Nature Communications · 2025-04-01 · 1 citations

  articleOpen access

  A broad chemical genetic screen in Mycobacterium tuberculosis (Mtb) identified compounds (BRD-8000.3 and BRD-9327) that inhibit the essential efflux pump EfpA. To understand the mechanisms of inhibition, we determined the structures of EfpA with these inhibitors bound at 2.7-3.4 Å resolution. Our structures reveal different mechanisms of inhibition by the two inhibitors. BRD-8000.3 binds in a tunnel contacting the lipid bilayer and extending toward the central cavity to displace the fatty acid chain of a lipid molecule bound in the apo structure, suggesting its blocking of an access route for a natural lipidic substrate. Meanwhile, BRD-9327 binds in the outer vestibule without complete blockade of the substrate path to the outside, suggesting its possible inhibition of the movement necessary for alternate access of the transporter. Our results show EfpA as a potential lipid transporter, explain the basis of the synergy of these inhibitors and their potential for combination anti-tuberculosis therapy.

  PublisherOA PDFDOI

• TamL is a Key Player of the Outer Membrane Homeostasis in Bacteroidota

  Journal of Molecular Biology · 2025-03-04 · 1 citations

  articleOpen access

  • In Proteobacteria, TamA and TamB form the TAM which assembles some autotransporters in the OM. • Unlike Proteobacteria, Bacteroidota encode TamL, a TamA-like lipoprotein. • In the Bacteroidota F. johnsoniae and C. canimorsus TamL and TamB are essential. • TamL depletion affects outer membrane permeability and protein but not lipid composition. • TamB co-purifies with TamL, suggesting an interaction to form a TAM complex. In Proteobacteria, the outer membrane protein TamA and the inner membrane-anchored protein TamB form the Translocation and Assembly Module (TAM) complex, which facilitates the transport of autotransporters, virulence factors, and likely lipids across the two membranes. In Bacteroidota, TamA is replaced by TamL, a TamA-like lipoprotein with a lipid modification at its N-terminus that likely anchors it to the outer membrane. This structural difference suggests that TamL may have a distinct function compared to TamA. However, the role of TAM in bacterial phyla other than Proteobacteria remains unexplored. Our study aimed to elucidate the function of TamL in Flavobacterium johnsoniae , an environmental Bacteroidota. Unlike its homologues in Proteobacteria, we found that TamL and TamB are essential in F. johnsoniae . Through genetic, phenotypic, proteomic, and lipidomic analyses, we show that TamL depletion severely compromises outer membrane integrity, as evidenced by reduced cell viability, altered cell shape, increased susceptibility to membrane-disrupting agents, and elevated levels of outer membrane lipoproteins. Notably, we did not observe an overall decrease in the levels of β-barrel outer membrane proteins, nor substantial alterations in outer membrane lipid composition. By pull-down assays, we found TamL co-purifying with TamB in F. johnsoniae , suggesting an interaction. Furthermore, we found that while TamL and TamB monocistronic genes are conserved among Bacteroidota, only some species encode multiple TamL, TamB and TamA proteins. To our knowledge, this study is the first to provide functional insights into a TAM subunit beyond Proteobacteria.

  PublisherDOI

• Synthesis of perfluorooctanoic acid-containing membrane lipids by human pathobionts

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-14

  preprintOpen access1st author

  Abstract Per- and polyfluoroalkyl substances (PFAS) are synthetic fluorinated compounds used widely in industrial and consumer products. They are unusually stable due to carbon–fluorine bonds and resistant to degradation, making them persistent contaminants in water, soil, and biota. PFAS are associated with adverse health effects in humans including cancer and liver disease. The effects of PFAS on human-associated bacteria are largely unexplored, a significant gap in knowledge because these bacteria are exposed to PFAS in vivo at sites including the colon and bladder. One of the best studied PFAS compounds is perfluorooctanoic acid (PFOA), an eight-carbon perfluorinated carboxylic acid whose structure is analogous to a fatty acid. Here, we cultured Enterococcus faecalis , a Gram-positive bacterium, and Pseudomonas aeruginosa , a Gram-negative bacterium, in growth medium supplemented with PFOA and corresponding control conditions and performed lipidomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate lipid remodeling in response to PFOA exposure. Strikingly, novel fluoroalkyl-containing membrane lipids are synthesized by both of these bacteria, with each species synthesizing unique fluoroalkyl-lipids. Moreover, a high-level daptomycin-resistant strain of E. faecalis produces strikingly high levels of fluoroalkyl-lipids, demonstrating that prior antibiotic exposure and concomitant effects on bacterial evolution can alter bacterial interactions with PFAS. Because bacterial lipids are important immunomodulators in vivo , we propose that PFAS-containing bacterial lipids may be novel mediators of host–microbe–pollutant interactions. Our results also establish a novel mechanism for the bioaccumulation of PFOA and, potentially, for bioremediation of PFOA in biological systems such as the human gastrointestinal tract.

  PublisherOA PDFDOI

• An IPN Bioink and Cross-Linking Process for Enhanced Mechanical Properties and Dynamic Control of Cell Spreading in 3D Bioprinting

  ACS Applied Engineering Materials · 2025-10-23

  article

  Most hydrogel-based 3D bioprinting results in mechanically soft and weak constructs that are not suitable for practical tissue engineering applications. Conventional approaches to increase the stiffness of hydrogels lead to entrapment of encapsulated cells and suboptimal biological responses. In this paper, we report on a bioprinting process that provides dynamic control over stiffness and strength of the printed cell–hydrogel constructs, which promote cell spreading. The biomaterial ink consists of gelatin, gelatin methacryloyl (GelMA), and alginate, with each component independently cross-linked by enzymatic, photo-, and ionic cross-linking, respectively, to form interpenetrating networks (IPNs). The formation of IPNs significantly improved the mechanical properties and chemical stability of the printed structures. Temporal control of each cross-linking mechanism significantly increased cell spreading, avoiding cell entrapment in the stiff 3D hydrogel environment, while improving the mechanical properties of the constructs. This bioink and cross-linking process is expected to become a useful tool for producing mechanically robust engineered tissues.

  PublisherDOI

• Laminin-Functionalized Gelatin Microgels for the Generation of Functional Neurons from Neural Progenitor Cells

  ACS Biomaterials Science & Engineering · 2025-05-29

  article

  The development of suitable hydrogels as delivery vehicles for neural stem/progenitor cells (NSPCs) is ongoing. Most injectable hydrogels for NSPC delivery either are mechanically fragile or do not promote the desired cell morphological changes during neural differentiation or cell-cell interactions during mature synapse formation. In this report, the utility of a gelatin microgel-based injectable hydrogel is explored for the encapsulation of NSPCs with the purpose of generating functional neurons. In addition, we describe facile enzymatic chemistry for the conjugation of bioactive proteins, such as laminin, to the surface of gelatin microgels to improve cell adhesion and organization of encapsulated cells. Encapsulation in the microgel assembly with immobilized laminin substantially improved NSPC viability compared with the nonporous hydrogel with the same chemical composition and resulted in enhanced neural differentiation (both neuronal and glial) with physiologically relevant morphological changes and cell-cell connections evidenced by immunofluorescence imaging. The firing of functional neurons when stimulated by glutamate was confirmed by calcium flux imaging after 4 weeks of differentiation. These results indicate the potential usage of gelatin microgels as an injectable formulation for NSPC delivery for neural tissue regeneration.

  PublisherDOI

• Biosynthesis of glucosaminyl phosphatidylglycerol in <i>Pseudomonas aeruginosa</i>

  Journal of Bacteriology · 2025-11-28

  articleOpen accessSenior author

  ABSTRACT Glucosaminyl phosphatidylglycerol (GlcN-PG) was first identified in bacteria in the 1960s and was recently reported in Pseudomonas aeruginosa . Despite the important implications in altering membrane charge (by the modification of anionic phosphatidylglycerol [PG] with cationic glucosamine), the biosynthesis and functions of GlcN-PG have remained uncharacterized. Using bioinformatic and lipidomic analysis, we identified a 3-gene predicted operon, renamed as gpgSDF , that is responsible for the biosynthesis and potential transport of GlcN-PG in P. aeruginosa: gpgS encodes a novel glycotransferase that is responsible for the modification of PG with N -acetylglucosamine (GlcNAc) to produce GlcNAc-PG, and gpgD encodes a novel deacetylase that removes the acetyl group from GlcNAc-PG to produce GlcN-PG. The third gene, gpgF , is predicted to encode a flippase whose activity remains to be experimentally verified. A P. aeruginosa gpgD transposon mutant accumulates GlcNAc-PG and lacks GlcN-PG, and as expected, the complementation of gpgD restores the production of GlcN-PG. Moreover, the heterologous expression of gpgSDF in Escherichia coli resulted in the production of both GlcNAc-PG and GlcN-PG. The identification of the biosynthetic genes of GlcN-PG paves the way for the investigation of its biological and pathological functions, which has significant implications in our understanding of the unique membrane physiology, pathogenesis, and antimicrobial resistance of P. aeruginosa . IMPORTANCE The identification of the biosynthetic genes of glucosaminyl phosphatidylglycerol (GlcN-PG) paves the way for the investigation of its biological and pathological functions, which has significant implications in our understanding of the unique membrane physiology, pathogenesis, and antimicrobial resistance of Pseudomonas aeruginosa .

  PublisherDOI

Recent grants

• Adaptive alterations of lipids in mitis group streptococci

  NIH · $2.5M · 2020–2026

• Roles of novel cationic lipids in bacterial pathogenesis

  NIH · $2.0M · 2023–2028

• NIH Grant U54GM069338

  NIH · $139.8M · 2014

• NIH Grant R56AI139105

  NIH · $479k · 2021

Frequent coauthors

• Christian R.H. Raetz

  175 shared

• Pei Zhou

  China Medical University

  62 shared

• Jerry Eichler

  Ben-Gurion University of the Negev

  48 shared

• Sheo B. Singh

  Stevens Institute of Technology

  48 shared

• Xiaoyuan Wang

  Shanghai Ocean University

  39 shared

• Kelli L. Palmer

  38 shared

• Jinshi Zhao

  Tianjin University of Technology

  37 shared

• Kithsiri Herath

  University of Maryland, Baltimore

  36 shared

Education

• Postdoc, Chemistry

  Cornell University

  1997

• PhD, Chemistry

  University of Texas at Austin

  1994