Life versus ‘biomass’—why application needs cell biology

Protoplasma, Sep 2016

Peter Nick

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Life versus ‘biomass’—why application needs cell biology

Protoplasma Life versus 'biomass'-why application needs cell biology P. Nick 0 0 Karlsruhe Institute of Technology , Karlsruhe , Germany - For centuries, biology had been driven by the desire to order and understand the multitude of life forms. However, the last century saw the discovery of unifying molecular principles for life, which caused a paradigm shift; now, molecules, rather than shape, were invoked to explain life. This molecular explanation of life not only shifted biology into the centre of scientific progress but also stimulated a vigorously developing new branch of technological application. The success of biotechnology demonstrated impressively that tools and concepts derived from chemistry could be employed to manipulate biology. Interestingly, over the entire first half of the last century, the breakthroughs of biochemistry were made on the base of quite simplistic concepts of the cell. Only from the 1950s, it became progressively clear that a cell is more than just a ‘bag of enzymes’. However, bioengineering still tends to speak about the cells growing in biofermenters as ‘biomass’. In his famous Science publication, Paul Srere (1967) compared enzyme concentrations in tissues, and he concluded that the local concentrations found in vivo are orders of magnitudes higher than those used in vitro. This was nothing else than the rehabilitation of space as relevant category also for molecular biology. In consequence, the spatial organisation of molecules and the compartmentalisation of metabolic activity become highly relevant, if one wants to understand and to manipulate biosynthetic pathways. The secondary metabolism of plants with its estimated more than a million specific molecules provides impressive examples for metabolic compartmentalisation. To exploit the biotechnological potential of this biochemical proficiency requires insight into the cell biological aspects. Several contributions in the current issue add new aspects that are relevant, if one wants to tailor the biotechnological use of plant secondary compounds. A central element of the chemical toolbox for secondary metabolites are the cytochrome P450 enzymes. This highly diverse group of proteins has virtually exploded during the evolution of terrestrial plants, giving rise to several hundreds of members in angiosperms. The cytochrome P450 proteins are endowed with a high substrate-specificity and often determine the time-limiting step of a pathway, driving oxidative and mostly irreversible reactions such as hydroxylations, epoxidations, dealkylations, dehydrations, or carbon-bond cleavages. The evolutionary background for the wealth of these enzymes has to be seen in the rich and sophisticated interactions entertained by terrestrial plants with other organisms. The review by Rasool and Rozi (2016) in the current issue gives an overlook of the current knowledge on this pacemaker of secondary metabolism focussing on examples with relevance to pharmacological applications such as the terpenoid indole alkaloids. On the examples of traditionally used medical plants such as Withania somnifera (Srivastava et al. 2015) , they illustrate how advances in genomics, if they are well integrated with cellular and regulatory viewpoints, can propel the biotechnological use of such secondary compounds to a new level. Many of the pharmaceutically interesting compounds produced by plants are derived from lipids, and the respective pathways are often strongly compartmentalised between different organelles. This involves considerable trafficking of lipids, an aspect that is often overlooked. Lipid transport is anything else than trivial in an aqueous environment. The review by Lung and Chye (2016) in the current issue shifts important players of this transport into the focus: the AcylCoA-binding proteins not only act as binding partners for important intermediates of lipid metabolism but also fulfil opens avenues for sophisticated tailoring. Since the pathway is activated by jasmonic acid, dependent on the transcriptional activator octadecanoid response Catharanthus AP2-domain protein, authors have used the strategy to overexpress this regulator under a glucocorticoid inducible promoter. Surprisingly, this did not stimulate the accumulation of the tested alkaloids, although the transcripts of all the synthetic enzymes were upregulated, with one exception. This exception was strictosidine glucosidase, which was downregulated, thus creating a bottleneck that was concluded to be responsible for the negative output of this approach. To overcome this limitation, the authors engineered strictosidine glucosidase under control of the same glucocorticoid inducible promoter. This time, their approach was successful yielding some 50 % of increase in the accumulation of the terpenoid indole alkaloids of interest. This work shows nicely that knowledge on the regulation of metabolic pathways directly translates into a better efficiency of biotechnological exploitation. Compliance with ethical standards Conflict of interest The author declares that he has no conflict of interest. Dostal V , Libusova L ( 2014 ) Microtubule drugs: action, selectivity, and resistance across the kingdoms of life . Protoplasma 251 : 991 - 1005 Lung SC , Chye ML ( 2016 ) Deciphering the roles of acyl-CoA-binding proteins in plant cells . Protoplasma , current issue Murphy DJ ( 2006 ) The extracellular pollen coat in members of the Brassicaceae: composition, biosynthesis, and functions in pollination . Protoplasma 228 : 31 - 39 Rasool S , Rozi M ( 2016 ) Plant cytochrome P450s: nomenclature and involvement in natural product biosynthesis . Protoplasma, current issue Srere PA ( 1967 ) Enzyme concentrations in tissues . Science 158 : 936 - 937 Srivastava S , Sangwan RS , Tripathi S , Mishra B , Narnoliya LK , Misra LN , Sangwan NS ( 2015 ) Light and auxin responsive cytochrome P450s from Withania somnifera Dunal: cloning, expression and molecular modelling of two pairs of homologue genes with differential regulation . Protoplasma 252 : 1421 - 1437 Sun J , Peebles C ( 2016 ) Engineering overexpression of ORCA3 and strictosidine glucosidase in Catharanthus roseus hairy roots increases alkaloid production . Protoplasma, current issue Verma P , Mathur AK , Srivastava A , Mathur A ( 2012 ) Emerging trends in research on spatial and temporal organization of terpenoid indole alkaloid pathway in Catharanthus roseus: a literature update . Protoplasma 249 : 255 - 268 Zhang M , Wang S , Li CX , Zhan YG , Yin J , Xiao JL , Liang T , Li X ( 2016 ) Molecular cloning and promoter analysis of squalene synthase and squalene epoxidase genes from Betula platyphylla . Protoplasma, current issue

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Peter Nick. Life versus ‘biomass’—why application needs cell biology, Protoplasma, 2016, 1175-1176, DOI: 10.1007/s00709-016-1014-7