About

Clay C.C. Wang, PhD, is a professor at USC Mann and serves as the chair of the Department of Pharmacology and Pharmaceutical Sciences. He also holds a joint appointment in the Department of Chemistry at the Dornsife College of Letters, Arts and Sciences. Dr. Wang received his BA in chemistry from Harvard University in 1996 and completed his PhD in chemistry at the California Institute of Technology in 2001. Following his doctoral studies, he completed a two-year postdoctoral fellowship in chemistry and chemical engineering at Stanford University. His research program focuses on the interface of chemistry and biological sciences, specifically exploring the mechanisms of natural product biosynthesis in bacteria and fungi. His laboratory investigates the use of Aspergillus nidulans as a host for producing fungal natural products and explores the potential of fungal hosts for upcycling plastics into high-value natural products. His areas of expertise include natural products, drug discovery, gene regulation of fungal secondary metabolism, sustainability, fungal and bacterial genomes, space biology, and metabolic engineering.

Research topics

• Biology
• Microbiology
• Genetics
• Computer Science
• Aeronautics
• Engineering
• Biochemistry
• Aerospace engineering
• Biochemical engineering
• Botany
• Physics
• Astrobiology

Selected publications

• Methylobacterium ajmalii sp. nov., Isolated From the International Space Station

  The Catalogue of Life · 2026-02-17

  datasetOpen access
  PublisherDOI

• Manipulation of Global Regulator <i>mcrA</i> Activates the Fumigermin Pathway in <i>Penicillium camemberti</i> IMV00769

  ACS Chemical Biology · 2026-02-11

  articleSenior authorCorresponding

  Fungal secondary metabolites have historically provided important applications in a variety of industries. Penicillium camemberti, a fungus with a role in cheese production, was domesticated to food use partly due to its metabolically depleted characteristic, minimizing the risk of toxic compound formation. However, antiSMASH analysis of the genome reveals that strains of the species do contain various cryptic biosynthetic gene clusters and, thus, have the potential capability of producing multiple secondary metabolites despite its limited compound production under normal laboratory conditions. Here, we genetically engineered Penicillium camemberti strain IMV00769, which is genetically similar to cheese-making isolates, by deleting negative global regulator, mcrA. This deletion resulted in the production of secondary metabolites not previously produced by this strain, including fumigermin, a compound patented for cosmetic applications for the reduction of skin wrinkles, enhancement of skin elasticity, and skin whitening. Our findings highlight the power of global regulator manipulation to activate cryptic biosynthetic pathways and expand the range of natural products accessible from domesticated fungal strains.

  PublisherDOI

• Metabolomics-driven rapid enrichment of candidate acetylcholinesterase-inhibitory metabolites from Clinacanthus nutans using a short-cycle callus culture platform

  Industrial Crops and Products · 2026-05-23

  articleOpen access

  • Short-cycle callus induction significantly remodels the C. nutans metabolome. • Medium optimization drives 20-fold feruloylagmatine enrichment within one week. • Leaf explants exhibit superior biosynthetic plasticity for bioactive markers. • Concurrent metabolite accumulation correlates with enhanced AChE inhibition. • In silico analysis suggests that feruloylagmatine possesses potential AChE-binding affinity, comparable or favorable to that of berberine. • The system ensures a standardized supply of high-value botanical raw materials.

  PublisherDOI

• Methylobacterium ajmalii sp. nov., Isolated From the International Space Station

  The Catalogue of Life · 2026-02-16

  datasetOpen access
  PublisherDOI

• Subspace-projected multireference covariant density functional theory

  Physical review. C · 2025-08-25 · 2 citations

  article

  Multireference density functional theory (MR-DFT) has been a pivotal method for studying nuclear low-lying states and neutrinoless double-beta ($0\ensuremath{\nu}\ensuremath{\beta}\ensuremath{\beta}$) decay. However, quantifying their theoretical uncertainties has been a significant challenge due to the computational demands. This study introduces a subspace-projected covariant density functional theory (SP-CDFT), which efficiently emulates MR-CDFT calculations for nuclear low-lying states. This approach leverages the eigenvector continuation method combined with the quantum-number projected generator coordinate method, based on a relativistic energy density functional (EDF). We apply SP-CDFT to investigate the correlations among the physical quantities of nuclear matter, nuclear low-lying spectroscopy, and the nuclear matrix elements (NMEs) of $0\ensuremath{\nu}\ensuremath{\beta}\ensuremath{\beta}$ decay in the two heaviest candidate nuclei. Our findings reveal generally strong correlations between the NMEs of $0\ensuremath{\nu}\ensuremath{\beta}\ensuremath{\beta}$ decay and the excitation energy of the ${2}_{1}^{+}$ state, as well as the $E2$ transition strength, although these correlations vary significantly among nuclei. This work also paves the way for refining nuclear EDF parameters using spectroscopic data.

  PublisherDOI

• Activation of the Trichodimerol Pathway through Deletion of <i>mcrA</i> in Marine <i>Penicillium rubens</i> YAP001

  ACS Chemical Biology · 2025-03-17 · 2 citations

  articleOpen accessSenior authorCorresponding

  Fungal secondary metabolites (SMs) are complex organic compounds comprising a variety of biological activities that are essential in medicine. These natural products can be found in various environments, with studies demonstrating the importance of studying marine-sourced fungi due to the increased potency of the compounds they produce. In this study, we sourced a Penicillium rubens YAP001 strain isolated from Exaiptasia diaphana and explored an avenue for the upregulation of its SMs by combining the one-strain-many-compounds (OSMAC) strategy with genetic manipulation of negative global regulator of secondary metabolism, mcrA. Here, we generated a mcrAΔ strain of marine P. rubens (YAP001), which led to the detection of sorbicillinoids, which is significant due to the prior discovery that these compounds illicit cytotoxic effects that have the potential as an anticancer agent. Specifically, we found that sorbicillin was not only upregulated but the mutant strain also produced the dimeric product, trichodimerol, which often exhibits stronger biological activities compared to sorbicillin. Furthermore, the reduced form of trichodimerol, dihydrotrichodimerol, was also detected in the mutant strain. This work suggests that genetic manipulation of global regulators in combination with the OSMAC method in filamentous fungi is a promising technique for upregulating pathways of interest for small-molecule drug discovery.

  PublisherOA PDFDOI

• Discovery of Uncommon Tryptophan-Containing Diketopiperazines from <i>Aspergillus homomorphus</i> CBS 101889 Using an <i>Aspergillus nidulans</i> Heterologous Expression System

  Journal of Natural Products · 2024-07-11 · 6 citations

  articleOpen accessCorresponding

  Fungal secondary metabolite (SM) biosynthetic gene clusters (BGCs) containing dimethylallyltryptophan synthases (DMATSs) produce structurally diverse prenylated indole alkaloids with wide-ranging activities that have vast potential as human therapeutics. To discover new natural products produced by DMATSs, we mined the Department of Energy Joint Genome Institute’s MycoCosm database for DMATS-containing BGCs. We found a DMATS BGC in Aspergillus homomorphus CBS 101889, which also contains a nonribosomal peptide synthetase (NRPS). This BGC appeared to have a previously unreported combination of genes, which suggested the cluster might make novel SMs. We refactored this BGC with highly inducible promoters into the model fungus Aspergillus nidulans. The expression of this refactored BGC in A. nidulans resulted in the production of eight tryptophan-containing diketopiperazines, six of which are new to science. We have named them homomorphins A–F (2, 4–8). Perhaps even more intriguingly, to our knowledge, this is the first discovery of C4-prenylated tryptophan-containing diketopiperazines and their derivatives. In addition, the NRPS from this BGC is the first described that has the ability to promiscuously combine tryptophan with either of two different amino acids, in this case, l-valine or l-allo-isoleucine.

  PublisherOA PDFDOI

• Transcription Factor Engineering in <i>Aspergillus nidulans</i> Leads to the Discovery of an Orsellinaldehyde Derivative Produced via an Unlinked Polyketide Synthase Gene

  Journal of Natural Products · 2024-09-27 · 2 citations

  articleOpen access

  Secondary metabolites are generally produced by enzymes encoded by genes within a biosynthetic gene cluster. Transcription factor genes are frequently located within these gene clusters. These transcription factors often drive expression of the other genes of the biosynthetic gene cluster, and overexpression of the transcription factor provides a facile approach to express all genes within a gene cluster, resulting in production of downstream metabolite(s). Unfortunately this approach is not always successful, leading us to engineer more effective hybrid transcription factors. Herein, we attempted to activate a putative cryptic biosynthetic gene cluster in Aspergillus nidulans using a combination of transcription factor engineering and overexpression approaches. This resulted in the discovery of a novel secondary metabolite we term triorsellinaldehyde. Surprisingly, deletion of the polyketide synthase gene within the gene cluster did not prevent triorsellinaldehyde production. However, targeted deletion of a polyketide synthase gene elsewhere in the genome revealed its role in triorsellinaldehyde biosynthesis.

  PublisherOA PDFDOI

• Discovery of penicillic acid as a chemical probe against tau aggregation in Alzheimer's disease

  Chemical Science · 2024-01-01 · 2 citations

  articleOpen accessSenior authorCorresponding

  experiments reveal that penicillic acid directly inhibits tau by disaggregating fibrils. Although penicillic acid possesses blood-brain barrier penetrability properties that are computationally predicted to be favorable, it is presumed to contain some mutagenic effects as well. To address this, we used the backbone of penicillic acid as a chemical probe to discover similar compounds that can inhibit AD tau aggregation with limited mutagenicity. This work suggests the potential of discovering chemical probes through natural product screening for small-molecule drug discovery of tauopathies.

  PublisherOA PDFDOI

• Subspace-projected multireference covariant density functional theory

  arXiv (Cornell University) · 2024-08-01

  preprintOpen access

  Multireference density functional theory (MR-DFT) has been a pivotal method for studying nuclear low-lying states and neutrinoless double-beta ($0νββ$) decay. However, quantifying their theoretical uncertainties has been a significant challenge due to the computational demands. This study introduces a subspace-projected covariant density functional theory (SP-CDFT), which efficiently emulates MR-CDFT calculations for nuclear low-lying states. This approach leverages the eigenvector continuation method combined with the quantum-number projected generator coordinate method, based on a relativistic energy density functional (EDF). We apply SP-CDFT to investigate the correlations among the physical quantities of nuclear matter, nuclear low-lying spectroscopy, and the nuclear matrix elements (NMEs) of $0νββ$ decay in the two heaviest candidate nuclei. Our findings reveal generally strong correlations between the NMEs of $0νββ$ decay and the excitation energy of the $2_1^+$ state, as well as the $E2$ transition strength, although these correlations vary significantly among nuclei. This work also paves the way for refining nuclear EDF parameters using spectroscopic data.

  PublisherOA PDFDOI

Recent grants

• NIH Grant P01GM084077

  NIH · $10.2M · 2015

• NIH Grant R01GM075857

  NIH · $834k · 2009

• NIH Grant F32GM065035

  NIH · $54k

• Exploiting interspecies/interkingdom communication for the discovery and development of novel natural products antifungal therapeutics

  NIH · $449k · 2016–2019

Frequent coauthors

• Yi‐Ming Chiang

  University of Southern California

  131 shared

• Berl R. Oakley

  University of Kansas

  98 shared

• Kenji Watanabe

  45 shared

• Nancy P. Keller

  University of Wisconsin–Madison

  42 shared

• James F. Sanchez

  City Of Hope National Medical Center

  37 shared

• Alex P. Praseuth

  Allergan (United States)

  32 shared

• Kinya Hotta

  30 shared

• Hideaki Oikawa

  Hokkaido University

  29 shared

Education

• Postdoctoral Fellowship

  Stanford University

  2003

• Ph.D., Chemistry

  California Institute of Technology

  2001

• AB, Chemistry

  Harvard University

  1996