[en] Enhancing lipid accumulation in microalgae is critical for commercial viability but often compromises growth. We previously generated through UV mutagenesis and iterative selection a Chlamydomonas reinhardtii mutant (H5) that retains parental growth while producing 3.2-fold more lipids (Sharma et al., 2015; Abdrabu et al., n.d.). Here, we present multi-omic analyses elucidating the molecular basis of this phenotype. Whole-genome sequencing revealed over 3000 mutations including a frameshift in the regulatory domain of 6-phosphofructokinase (PFK1). Six independent CLiP mutants in affected genes also showed elevated lipids, including a PFK1 mutant, validating functional relevance. Transcriptomics revealed upregulation of glycolytic genes and nutrient acquisition pathways under nutrient-replete conditions. Metabolomics identified an 8.31-fold malonate increase (p = 8.5 × 10−4), linking glycolysis to lipid synthesis. Lipidomics showed increased TAG diversity and lack of betaine lipids. Epigenomics revealed genome-wide hypermethylation, potentially stabilizing the phenotype. Together, these data suggest PFK1 deregulation drives metabolic reprogramming enabling lipid accumulation without growth penalty, demonstrating how evolutionary selection generates sophisticated metabolic solutions for engineering industrial microalgal strains.
Disciplines :
Environmental sciences & ecology
Author, co-author :
Nelson, David R.; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Chaiboonchoe, Amphun; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates ; Siriraj Center of Research Excellence for Precision Medicine and Systems Pharmacology (SiCORE-PM&SP), Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
Fu, Weiqi; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates ; State Key Laboratory of Ocean Sensing & Ocean College, Zhejiang University, Zhoushan, China
Khraiwesh, Basel; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates ; Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Dohai, Bushra; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates ; Institute of Network Biology (INET), Molecular Targets and Therapeutics Center (MTTC), Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany
Jaiswal, Ashish; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Al-Khairy, Dina; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Mystikou, Alexandra; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates ; Omics Centre of Excellence, Abu Dhabi, United Arab Emirates
Al Nahyan, Latifa; Al Yasmina Academy, Abu Dhabi, United Arab Emirates
Amnah Salem Jumah Mohamed Alzahmi ; Université de Liège - ULiège > TERRA Research Centre ; NYU Abu Dhabi - New York University Abu Dhabi > Division of Science
Nayfeh, Layanne; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Daakour, Sarah ; Université de Liège - ULiège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Biologie cellulaire et moléculaire ; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
O'Connor, Matthew J.; Core Technology Platform (CTP) Operations, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Sultana, Mehar; Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi, Abu Dhabi, United Arab Emirates ; Core Technology Platform (CTP) Operations, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Hazzouri, Khaled M.; Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi, Abu Dhabi, United Arab Emirates ; Khalifa Center for Genetic Engineering and Biotechnology (KCGEB), UAE University, Abu Dhabi, United Arab Emirates
Twizere, Jean-Claude ; Université de Liège - ULiège > GIGA > GIGA Molecular & Computational Biology - Viral Interactomes Network ; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Salehi-Ashtiani, Kourosh; Division of Science, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
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