ArticleProceedings of the National Academy of Sciences of the United States of America2012
Identification and treatment of heme depletion attributed to overexpression of a lineage of evolved P450 monooxygenases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 88 citations in OpenAlex.
- TOR kinase inhibition reverses azole resistance in Candida auris by targeting heme biosynthesis.Archives of microbiology · 2026Article
- The Hemoprotein Hhy1 Promotes Heme-Dependent Catalase Activity of Ctt1.Molecular microbiology · 2026Article
- Engineering Saccharomyces cerevisiae to improve heterologous abscisic acid production.Microbial cell factories · 2026Article
- A novel P450 enzyme assay utilizing an NADPBiotechnology letters · 2025Article
- The heme-regulated inhibitor kinase Hri1 is activated in response to aminolevulinic acid deficiency in Schizosaccharomyces pombe.PLoS genetics · 2025Article
- Functional Differentiation and Regulatory Mechanisms of Ferrochelatases HemH1 and HemH2 inInternational journal of molecular sciences · 2025Article
- Metabolic engineering of yeast to efficiently synthesize heme and hemoproteins: recent advance and prospects.FEMS yeast research · 2025Review
- Modeling for understanding and engineering metabolism.QRB discovery · 2025Article
- Engineering the microenvironment of P450s to enhance the production of diterpenoids inActa pharmaceutica Sinica. B · 2024Article
- Metabolic engineering of Saccharomyces cerevisiae for chelerythrine biosynthesis.Microbial cell factories · 2024Article
- Strategies, Achievements, and Potential Challenges of Plant and Microbial Chassis in the Biosynthesis of Plant Secondary Metabolites.Molecules (Basel, Switzerland) · 2024Review
- Edible mycelium bioengineered for enhanced nutritional value and sensory appeal using a modular synthetic biology toolkit.Nature communications · 2024Article
- Pseudomonas putida as a platform for medium-chain length α,ω-diol production: Opportunities and challenges.Microbial biotechnology · 2024Article
- Reconstitution of early paclitaxel biosynthetic network.Nature communications · 2024Article
- Fluorometric Methods to Measure Bioavailable and Total Heme.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Efficient stereoselective hydroxylation of deoxycholic acid by the robust whole-cell cytochrome P450 CYP107D1 biocatalyst.Synthetic and systems biotechnology · 2023Article
- Biosynthesis of High-Active Hemoproteins by the Efficient Heme-Supply Pichia Pastoris Chassis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Increasing lysergic acid levels for ergot alkaloid biosynthesis: Directing catalysisFrontiers in microbiology · 2023Article
- Exploring optimal Taxol® CYP725A4 activity in Saccharomyces cerevisiae.Microbial cell factories · 2022Article
- A haem-sequestering plant peptide promotes iron uptake in symbiotic bacteria.Nature microbiology · 2022Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Recent advances in metabolic engineering have demonstrated that microbial biosynthesis can provide a viable alternative to chemical synthesis for the production of bulk and fine chemicals. Introduction of a new biosynthetic pathway typically requires the expression of multiple heterologous enzymes in the production host, which can impose stress on the host cell and, thereby, limit performance of the pathway. Unfortunately, analysis and treatment of the host stress response can be difficult, because there are many sources of stress that may interact in complex ways. We use a systems biological approach to analyze the stress imposed by expressing different enzyme variants from a lineage of soluble P450 monooxygenases, previously evolved for heterologous activity in Saccharomyces cerevisiae. Our analysis identifies patterns of stress imposed on the host by heterologous enzyme overexpression that are consistent across the evolutionary lineage, ultimately implicating heme depletion as the major stress. We show that the monooxygenase evolution, starting from conditions of either high or low stress, caused the cellular stress to converge to a common level. Overexpression of rate-limiting enzymes in the endogenous heme biosynthetic pathway alleviates the stress imposed by expression of the P450 monooxygenases and increases the enzymatic activity of the final evolved P450 by an additional 2.3-fold. Heme overexpression also increases the total activity of an endogenous cytosolic heme-containing catalase but not a heterologous P450 that is membrane-associated. This work demonstrates the utility of combining systems and synthetic biology to analyze and optimize heterologous enzyme expression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.