- Anastasios Melis
- Photosynthesis, Metabolic Engineering, Synthetic Biology, Bioenergy Research
- Professor of Plant & Microbial Biology, and Editor-in-Chief, Planta
- 471A Koshland Hall
- Berkeley, California 94720
- Phone 510.642.8166
- Lab Phone 510.642.6209
- Fax 510.642.4995
- B.Sc. University of AthensPh.D. Florida State UniversityPostdoctoral training: Rijksuniversiteit Leiden, The NetherlandsPostdoctoral training: Carnegie Institution for Science, Stanford, CA
We study the photosynthesis of plants, microalgae, cyanobacteria, and photosynthetic bacteria. Approaches include biophysics and biochemistry of the process, molecular biology and genetics of the organisms, and scale ups for product generation. Applied aspects include diverting the flow of photosynthesis to generate high-value compounds instead of the normally produced sugars. Products of interest are biofuels, feedstock for the synthetic chemistry industry and pharmaceuticals. Our trademark is product generation directly from photosynthesis, bypassing the need to harvest and process the respective biomass.
Photosynthetic Biofuels and Chemicals
Expertise and Philosophy
The expertise of the Melis lab is in the field of photosynthesis and metabolism. We work with land plants, microalgae, cyanobacteria, and non-oxygenic (anaerobic) photosynthetic bacteria. Our platform includes most aspects of photosynthesis, beginning with organism cultivation, the efficiency of light absorption and utilization, electron transport and biochemical energy generation, and chloroplast and cellular metabolism. Included are the biophysics and biochemistry of the process, the molecular biology and genetics of the organisms, as well as scale ups in the cultivation of the various organisms for product generation.
The concept of “Photosynthetic Biofuels”, envisioned and pioneered by us, entails the direct application of photosynthesis for the generation of fuels and related chemicals, in a process where a single organism acts both as catalyst and processor, synthesizing and secreting ready to use commodity products.
The lab contributed with a breakthrough in the field, when in 2000 we demonstrated, for the first time, how to divert the natural flow of photosynthesis in green microalgae and to sustainably generate hydrogen gas, instead of the normally produced oxygen. This technology is currently employed by many laboratories in several countries, and serves as the platform for further photobiological hydrogen production research in the field.
The Melis lab also pioneered and currently leads an international effort to improve, by up to 300%, the efficiency and productivity of photosynthesis in mass cultures under bright sunlight conditions. This is implemented upon genetically optimizing the size of the array of chlorophyll molecules that serve as antennae to absorb sunlight for the photosynthetic apparatus.
In 2010, the Melis lab pioneered yet a new platform for the renewable generation of isoprene (C5H8) hydrocarbons in cyanobacteria and microalgae, derived entirely from sunlight, carbon dioxide (CO2) and water (H2O), and generated immediately from the primary products of photosynthesis. The process of generating isoprene currently serves as a case study in the development of technologies for the renewable generation of a multitude of biofuels and other useful bio-products.
Hydrogen and hydrocarbon fuel and chemicals production via the process of photosynthesisReprogramming photosynthetic carbon flow in plants, microalgae, and cyanobacteria enabled the heterologous generation of fuel and chemicals as clean, renewable and economically viable commodities. However, specific biological problems associated with a sustained, high yield photosynthetic production of these compounds remain to be addressed.
- Maximize the solar-to-biomass energy conversion efficiency of photosynthesis in plants, microalgae, and cyanobacteria cultivated under high mass-culture or canopy-density conditions.
- Apply metabolic engineering approaches to enhance carbon partitioning in photosynthetic organisms toward greater terpenoid biosynthesis.
- Improve the yield of terpene hydrocarbons in plants, microalgae, and cyanobacterial production systems and exploit their photosynthesis for direct "essential oils" production.
- Develop and apply innovative photobioreactor concepts for renewable fuel and chemicals production.
Application of the TLA Concept to Enhance the Solar-to-Biomass Energy Conversion Efficiency of Photosynthesis
The Melis lab has pioneered in plants, microalgae, and cyanobacteria the concept of a Truncated Light-harvesting chlorophyll Antenna size. Such TLA-strains show improved solar-to-biomass energy conversion efficiency of photosynthesis under bright sunlight conditions. The objective of the TLA effort is to approach the theoretical maximum of 8-10% solar-to-biomass energy converion efficiency of photosynthesis, an improvement of up to 300% over the best-case efficiency scenario currrently observed with wild type couterparts.
Schematic presentation of incident sunlight absorption and processing by fully pigmented (dark green) microalgae in a high-density culture. Individual cells at the surface of the culture would over-absorb incoming sunlight (more than can be utilized by photosynthesis), and dissipate most of it via non-photochemical quenching (NPQ), thus limiting productivity (P). Note that a high probability of absorption by the first layer of cells would cause shading, i.e., prevent cells deeper in the culture from being exposed to sunlight.
Schematic presentation of incident sunlight absorption and processing through cells with a truncated chlorophyll antenna size. Individual cells have a diminished probability of absorbing sunlight, thereby permitting greater penetration and a more uniform distribution of irradiance through the culture. This alleviates NPQ and enhances photosynthetic productivity (P) by the culture as a whole. (From Melis, 2009.)
A hydrogen-producing Chlamydomonas reinhardtii culture. Hydrogen bubbles emanate toward the surface of the liquid medium. The gas is drained through a syringe (inserted in the middle of the silicone stopper) and, through Teflon tubing, is collected in an inverted burette and measured by the method of water displacement. Photograph courtesy of Michael Barnes, University of California, Office of the President. (From Melis and Happe, 2001.)
Through its Oleomics™ Project, the Melis Lab seeks to identify and exploit genes, enzymens, and biosynthetic pathways leading to "essential oils", including hydrocarbons for fuel and synthetic chemictry feedstock via the photosynthesis of plants, microalgae, and cyanobacteria.
Schematic of metabolic pathways in Synechocystis transformants, as employed in our work. Photosynthetically assimilated CO2 yields 3-phosphoglyceric acid (3PGA), which is converted into glyceraldehyde 3-phosphate (G3P) or pyruvate. Pyruvate and G3P are the primary reactants of the Synechocystis endogenous methylerythritol (MEP) biosynthetic pathway leading to the synthesis of the 5-carbon intermediates isopentenyl-diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Pyruvate decarboxylation leads to acetyl-CoA formation, which is the primary reactant of the heterologous mevalonic acid (MVA) pathway, also leading to the synthesis of IPP and DMAPP. Covalent linkage of IPP and DMAPP yields geranyl-diphosphate, a 10-carbon terpenoid intermediate metabolite, en route toward the generation of longer chain endogenous terpenoids (carotenoids, phytol, and quinone prenyl tails, among other). Heterologous expression of the PHLS gene drains a portion of the GPP pool toward the synthesis of β-phellandrene that spontaneously diffuses out of the cyanobacterial cell. The flow of endogenous carbon substrate toward the terpenoid biosynthetic pathway was enhanced upon heterologous expression of the MVA pathway in Synechocystis, increasing the pool size of IPP and DMAPP substrate. Endogenous and heterologous reactions are delineated in black and red, respectively. (From Formighieri and Melis, 2016.)
Custom-designed fed-batch bioreactor for diffusion-based gas exchange and terpene hydrocarbons production. A 100% carbon dioxide gas stream was slowly fed into the gaseous/aqueous two-phase bioreactor via the aerator tube to fill the reactor headspace. Efficient and spontaneous uptake and assimilation of headspace carbon dioxide by the cells occurred by diffusion and was concomitantly exchanged for photosynthetically produced oxygen and terpene hydrocarbons during photoautotrophic growth. Beta-phellandrene hydrocarbons accumulate as floater molecules on the surface of the aqueous phase in the sealed bioreactor. (From Bentley and Melis, 2012.)
Eroglu E, Okada S, Melis A (2011) Hydrocarbon productivities in different Botryococcus strains: comparative methods in product quantification. J Appl Phycol 23:763–775Ort DR, Zhu X-G, Melis A (2011) Optimizing antenna size to maximize photosynthetic efficiency. Plant Physiol. 155(1):79-85Blankenship RE, Tiede DM, Barber J, Brudvig GW, Fleming G, Ghirardi ML, Gunner MR, Junge W, Kramer DM, Melis A, Moore TA, Moser CC, Nocera DG, Nozik AJ, Ort DR, Parson WW, Prince RC, Sayre RT (2011) Comparing photosynthetic and photovoltaic efficiencies and recognizing the potential for improvement. Science 332:805-809Melis A (2011) Short chain volatile hydrocarbon production using genetically engineered microalgae, cyanobacteria or bacteria. United States Patent 7,947,478 (green microalgae; issued 24-May-2011)Bentley FK, Melis A (2012) Diffusion-based process for carbon dioxide uptake and isoprene emission in gaseous/aqueous two-phase photobioreactors by photosynthetic microorganisms. Biotech Bioeng 109:100-109Mitra M, Ng S, Melis A (2012) The TLA1 protein family members contain a variant of the plain MOV34/MPN domain. Amer J Biochem Mol Biol. 2(1): 1-18Melis A (2012) Photosynthesis-to-Fuels: From sunlight to hydrogen, isoprene, and botryococcene production. Energy Environ. Sci. 5(2): 5531-5539Kirst H, Garcia-Cerdan JG, Zurbriggen A, Melis A (2012) Assembly of the light-harvesting chlorophyll antenna in the green alga Chlamydomonas reinhardtii requires expression of the TLA2-CpFTSY gene. Plant Physiol 158: 930–945Mitra M, Dewez D, García-Cerdán JG, Melis A (2012) Polyclonal antibodies against the TLA1 protein also recognize with high specificity the D2 reaction center protein of PSII in the green alga Chlamydomonas reinhardtii. Photosynth Res 112:39-47Melis A (2012) Short chain volatile hydrocarbon production using genetically engineered microalgae, cyanobacteria or bacteria. United States Patent 8,133,708 (cyanobacteria; issued 13-Mar-2012)Zurbriggen A, Kirst H, Melis A (2012) Isoprene production via the mevalonic acid pathway in Escherichia coli (Bacteria). BioEnergy Res 5(4): 814-828, DOI 10.1007/s12155-012-9192-4Hong S-Y, Zurbriggen A, Melis A (2012) Isoprene hydrocarbons production upon heterologous transformation of Saccharomyces cerevisiae. J Appl Microbiol 113: 52-65Xie D-Y, Melis A (2012) Special Issue on metabolic plant biology (Editorial). Planta 236:763–764Kirst H, Garcia-Cerdan JG, Zurbriggen A, Ruehle T, Melis A (2012) Truncated photosystem chlorophyll antenna size in the green microalga Chlamydomonas reinhardtii upon deletion of the TLA3-CpSRP43 gene. Plant Physiol. 160(4):2251-2260Mitra M, Kirst H, Dewez D, Melis A (2012) Modulation of the light-harvesting chlorophyll antenna size in Chlamydomonas reinhardtii by TLA1 gene over-expression and RNA interference. Phil. Trans. R. Soc. B 367:3430-3443Bentley FK, García-Cerdán JG, Chen H-C, Melis A (2013) Paradigm of monoterpene (β-phellandrene) hydrocarbons production via photosynthesis in cyanobacteria. BioEnergy Res. 6:917–929; DOI: 10.1007/s12155-013-9325-4Melis A (2013) Carbon partitioning in photosynthesis. Curr Opin Chem Biol. 17:453–456; http://dx.doi.org/10.1016/j.cbpa.2013.03.010Chen H-C, Melis A (2013) Marker-free genetic engineering of the chloroplast in the green microalga Chlamydomonas reinhardtii. Plant Biotech J. 11: 818–828; DOI: 10.1111/pbi.12073Kirst H, Melis A (2014) The chloroplast Signal Recognition Particle pathway (CpSRP) as a tool to minimize chlorophyll antenna size and maximize photosynthetic productivity. Biotechnology Advances 32: 66–72Bentley FK, Zurbriggen A, Melis A (2014) Heterologous expression of the mevalonic acid pathway in cyanobacteria enhances endogenous carbon partitioning to isoprene. Molecular Plant 7:71-86Formighieri C, Melis A (2014) Regulation of β‑phellandrene synthase gene expression, recombinant protein accumulation, and monoterpene hydrocarbons production in Synechocystis transformants. Planta DOI: 10.1007/s00425-014-2080-8 in pressKirst H, Formighieri C, Melis A (2014) Maximizing photosynthetic efficiency and culture productivity in cyanobacteria upon minimizing the phycobilisome light-harvesting antenna size. Biochim Biophys Acta - Bioenergetics 1837(10):1653-1664Melis A, Lindberg P (2014) Isoprene hydrocarbon production using genetically engineered cyanobacteria. United States Patent 8,802,407 (issued 12-August-2014)Formighieri C, Melis A (2014) Carbon partitioning to the terpenoid biosynthetic pathway enables heterologous β‑phellandrene production in Escherichia coli cultures. Arch Microbiol 196(12):853-861 DOI 10.1007/s00203-014-1024-9Chaves JE, Kirst H, Melis A (2015) Isoprene production in Synechocystis under alkaline and saline growth conditions. J Appl Phycol 27:1089–1097 DOI: 10.1007/s10811-014-0395-2Melis A, Bentley FK, Wintz H-C Chen (2015) Continuous diffusion based method of cultivating photosynthetic microorganisms in a sealed photobioreactor to obtain volatile hydrocarbons. United States Patent 8,993,290 (issued 31-March-2015).Formighieri C, Melis A (2015) A phycocyanin·phellandrene synthase fusion enhances recombinant protein expression and β-phellandrene (monoterpene) hydrocarbons production in Synechocystis (cyanobacteria). Metab Eng 32:116–124 http://dx.doi.org/10.1016/j.ymben.2015.09.010Formighieri C, Melis A (2016) Sustainable heterologous production of terpene hydrocarbons in cyanobacteria. Photosynth Res. In press doi:10.1007/s11120-016-0233-2
Honors and AwardsElection to the rank of Fellow, American Association for the Advancement of Science - 2011Research Achievement Award - US Department of Energy, Hydrogen Program - 2004University Research Award - DaimlerChrysler Corporation - 2003Distinguished Teaching Award - College of Natural Resources - 1994