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The production of secondary metabolites from medicinal plants, also called Plant-Derived Medicinal Compounds (PDMC), is gaining ground in the last decade. Concomitant to the increase in the knowledge about the pharmacological properties of these compounds, horticultural plants are becoming the most important, sustainable and low-cost biomass source to obtain high-complex PDMCs to be used as medicaments. Biotechnological tools, including plant cell and tissue culture and plant genetic transformation, are increasingly being employed to produce high quality and rare PDMC under in vitro conditions. The proper use of these technologies requires studies in organogenesis to allow for better control of in vitro plant development and, thus, to the production of specific tissues and activation of the biochemical routes that result in the biosynthesis of the target PDMCs. Either biotic or abiotic factors, called elicitors, are responsible for triggering the PDMC synthesis. In vitro techniques, when compared to the conventional cultivation of medicinal plants in greenhouse or in the field, have the advantages of (1) producing PDMCs in sterile and controlled environmental conditions, allowing better control of the developmental processes, such as organogenesis, and (2) producing tissues with high PDMC contents, due to the efficient use of different biotic and abiotic elicitors. Nevertheless, the process has many challenges, e.g., the establishment of step-by-step protocols for in vitro biomass and PDMC production, both involving and being affected by many factors. Other limitations are the high costs in opposition to the relatively cheaper alternative of growing medicinal plants conventionally. This paper aims to quickly review the general origin of plant secondary metabolites, the leading techniques and recent advances for PDMC in vitro production, and the challenges around the use of this promising technology. Keywords: plant-derived medicinal compounds, in vitro cell and tissue culture, techniques, biotic and abiotic factors, biofactories Resumo Avancos e desafios na producao in vitro de metabolitos secundarios de plantas medicinais A producao de metabolitos secundarios de plantas medicinais, tambem chamados de Compostos Medicinais Derivados de Plantas (PDMC), vem ganhando importância na ultima decada. Concomitante ao aumento do conhecimento sobre as propriedades farmacologicas destes compostos, as plantas da horticultura tornam-se a fonte de biomassa mais importante, sustentavel e de baixo custo para a obtencao de PDMCs de alta complexidade a serem utilizados como medicamentos. Ferramentas biotecnologicas, incluindo cultura de celulas e tecidos e transformacao genetica, estao sendo cada vez mais empregadas para produzir PDMCs raros e de alta qualidade sob condicoes in vitro . O uso adequado dessas tecnologias requer estudos em organogenese para permitir um melhor controle do desenvolvimento in vitro das plantas e, assim, da producao de tecidos especificos e ativacao das rotas bioquimicas que resultam na biossintese dos PDMCs alvo. Elicitores bioticos ou abioticos sao responsaveis por desencadear a sintese desses PDMCs. As tecnicas de producao in vitro , quando comparadas ao cultivo convencional de plantas medicinais em casa de vegetacao ou no campo, tem as vantagens de (1) produzir PDMCs em condicoes ambientais estereis e controladas, permitindo um melhor controle de processos de desenvolvimento, como a organogenese, e (2) produzir tecidos com alto teor de PDMCs, devido a aplicacao eficiente de diferentes elicitores. No entanto, o processo tem muitos desafios como, por exemplo, o estabelecimento de protocolos para producao in vitro de biomassa e PDMC, ambos envolvendo e sendo afetados por muitos fatores. Outras limitacoes sao os altos custos em oposicao a alternativa relativamente mais barata de cultivar plantas medicinais convencionalmente. O objetivo deste artigo e revisar brevemente a origem dos metabolitos secundarios das plantas, as principais tecnicas e avancos recentes para a producao in vitro de PDMCs e os desafios em torno do uso dessa tecnologia promissora. Palavras-chave: compostos medicinais derivados de plantas, cultura de celulas e tecidos in vitro , tecnicas, fatores bioticos e abioticos, biofabricas.

Advances and challenges on the in vitro production of secondary metabolites from medicinal plants