02698nas a2200325 4500008004100000022001400041245006800055210006800123260000900191300001400200490000700214520169800221653001801919653002501937653002401962653001201986653002801998653002902026100002102055700002602076700001902102700002102121700002002142700002002162700002002182700002002202700002402222700002702246856009902273 2024 eng d a1674-205200aSteroidal scaffold decorations in Solanum alkaloid biosynthesis0 aSteroidal scaffold decorations in Solanum alkaloid biosynthesis cAUG  a1236-12540 v173 a

Steroidal glycoalkaloids (SGAs) are specialized metabolites produced by hundreds of Solanum species, including important vegetable crops such as tomato, potato, and eggplant. Although it has been known that SGAs play important roles in defense in plants and ``anti-nutritional''effects (e.g., toxicity and bitterness) to humans, many of these molecules have documented anti-cancer, anti-microbial, antiinflammatory, anti-viral, and anti-pyretic activities. Among these, a-solasonine and a-solamargine isolated from black nightshade (Solanum nigrum) are reported to have potent anti-tumor, anti-proliferative, and anti-inflammatory activities. Notably, a-solasonine and a-solamargine, along with the core steroidal aglycone solasodine, are the most widespread SGAs produced among the Solanum plants. However, it is still unknown how plants synthesize these bioactive steroidal molecules. Through comparative metabolomictranscriptome-guided approach, biosynthetic logic, combinatorial expression in Nicotiana benthamiana, and functional recombinant enzyme assays, here we report the discovery of 12 enzymes from S. nigrum that converts the starting cholesterol precursor to solasodine aglycone, and the downstream a-solasonine, a-solamargine, and malonyl-solamargine SGA products. We further identified six enzymes from cultivated eggplant that catalyze the production of a-solasonine, a-solamargine, and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation decorations. Our work provides the gene tool box and platform for engineering the production of high-value, steroidal bioactive molecules in heterologous hosts using synthetic biology.

10aa-solamargine10aBiosynthetic pathway10amalonyl-solamargine10aSolanum10aSpecialized metabolites10asteroidal glycoalkaloids1 aLucier, Rosalind1 aKamileen, Mohamed, O.1 aNakamura, Yoko1 aSerediuk, Sofiia1 aBarbole, Ranjit1 aWurlitzer, Jens1 aKunert, Maritta1 aHeinicke, Sarah1 aO'Connor, Sarah, E.1 aSonawane, Prashant, D. uhttp://library.ncl.res.in/content/steroidal-scaffold-decorations-solanum-alkaloid-biosynthesis02421nas a2200301 4500008004100000022001400041245011200055210006900167260000800236300001100244490000800255520141300263653002501676653001501701653002201716653001501738653002701753653002101780100002401801700002701825700002401852700002001876700002701896700002401923700002401947700002301971856012501994 2024 eng d a0926-669000aUnlocking the genetic and biotechnological potential of Gloriosa superba to enhance its alkaloid production0 aUnlocking the genetic and biotechnological potential of Gloriosa cMAY a1181440 v2113 a

Gloriosa superba is a medicinally important plant that produces the pharmaceutically precious colchicine molecule. Colchicine is being used for treating gout, for enhancing the production of interleukin-8 (inhibits human pancreatic cancer) and many other human ailments. Since its seeds and rhizomes (tuberous roots) are the chief sources of colchicine, pharmaceutical industries exploit the natural sources, thus demolishing its habitat. Chemo- and genetic diversity among the G. superba populations exist, but has not been exploited profitably. Scope exists for generating mutants using the chemical mutagens and also via breeding methods to generate superior varieties for commercial cultivation. Innovative methods for breaking seed dormancy and superior colchicine extraction, besides biotechnological interventions are imperative to save the biodiversity and to produce colchicine on a large scale. Biorhizomes produced in vitro hold great promise for biomanufacturing colchicine in bioreactors commercially. Since the biosynthetic pathway of colchicine is now known, isolation of the pathway genes and their heterologous overexpression or the application of synthetic biology methods needs to be explored in future for industrial manufacturing of colchicine. Advances made in the recent past in these fields of colchicine production from G. superba are critically evaluated in this review.

10aBiosynthetic pathway10aColchicine10aGenetic diversity10aGlory lily10aMetabolite elicitation10aOmics approaches1 aMahajan, Yogesh, A.1 aShinde, Balkrishna, A.1 aShirke, Harshad, A.1 aGandra, Jawahar1 aSuravajhala, Prashanth1 aKishor, P., B. Kavi1 aKadoo, Narendra, Y.1 aNikam, Tukaram, D. uhttp://library.ncl.res.in/content/unlocking-genetic-and-biotechnological-potential-gloriosa-superba-enhance-its-alkaloid02665nas a2200241 4500008004100000022001400041245009700055210006900152260000800221300001100229490000800240520185700248653002502105653002002130653002002150653002602170653001602196100002302212700002802235700002002263700001902283856012102302 2025 eng d a0960-741200aNavigating the challenges of engineering composite specialized metabolite pathways in plants0 aNavigating the challenges of engineering composite specialized m cMAR ae701000 v1213 a

Plants are a valuable source of diverse specialized metabolites with numerous applications. However, these compounds are often produced in limited quantities, particularly under unfavorable ecological conditions. To achieve sufficient levels of target metabolites, alternative strategies such as pathway engineering in heterologous systems like microbes (e.g., bacteria and fungi) or cell-free systems can be employed. Another approach is plant engineering, which aims to either enhance the native production in the original plant or reconstruct the target pathway in a model plant system. Although increasing metabolite production in the native plant is a promising strategy, these source plants are often exotic and pose significant challenges for genetic manipulation. Effective pathway engineering requires comprehensive prior knowledge of the genes and enzymes involved, as well as the precursor, intermediate, branching, and final metabolites. Thus, a thorough elucidation of the biosynthetic pathway is closely linked to successful metabolic engineering in host or model systems. In this review, we highlight recent advances in strategies for biosynthetic pathway elucidation and metabolic engineering. We focus on efforts to engineer complex, multi-step pathways that require the expression of at least eight genes for transient and three genes for stable transformation. Reports on the engineering of complex pathways in stably transformed plants remain relatively scarce. We discuss the major hurdles in pathway elucidation and strategies for overcoming them, followed by an overview of achievements, challenges, and solutions in pathway reconstitution through metabolic engineering. Recent advances including computer-based predictions offer valuable platforms for the sustainable production of specialized metabolites in plants.

10aBiosynthetic pathway10aEnzyme activity10aGene expression10aMetabolic engineering10aMetabolites1 aGharat, Sachin, A.1 aTamhane, Vaijayanti, A.1 aGiri, Ashok, P.1 aAharoni, Asaph uhttp://library.ncl.res.in/content/navigating-challenges-engineering-composite-specialized-metabolite-pathways-plants