The Lure of Beauty products

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The fashion and beauty sectors are witnessing an unprecedented era of growth and globalisation. In 2022, the beauty market—defined as skincare, fragrance, makeup, and haircare—generated approximately $430 billion in revenue and is expected to reach around $580 billion by 2027, growing at a projected 6% per year ^[1]. The glow of the beauty industry has proved hard to resist, attracting many new companies and investors.

Fig.1. Growth of the beauty market from 2022 to 2027.

Cosmetics

Cosmetics are a prime element in complementing an individual’s inherent beauty and physical features. Cosmetics also allow for personal style expression, making them a significant form of social expression. The global trend of self-care and grooming has surged in recent years, with beauty products helping individuals look healthier and more attractive, hence boosting their self-confidence, which is, in turn, propelling the cosmetics industry's growth.

Fragrance

The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. With increasing disposable incomes, the demand for luxury perfumes and fragrances is on the rise among consumers. These products are now seen as essential elements of personal hygiene and style statements. Consequently, there is a growing preference for natural, high-quality, long-lasting scents ^[2],[3].

Fig.2. The global perfume market size reached US$ 37.6 Billion in 2023. Looking forward, IMARC Group expects the market to reach US$ 60.1 Billion by 2032, exhibiting a growth rate (CAGR) of 5.2% during 2024-2032 ^[4].

In a nutshell, these products have aptly captured people's attention, starting from millennials to Gen-alpha. Skincare, haircare, makeup, perfumes, etc., are not just commodities...it’s a lifestyle!

But at what cost are these products manufactured?

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While the COVID-19 pandemic catalysed a significant increase in skincare and self-care awareness among both men and women globally, the rising popularity of the beauty industry can be credited to its highly consumer-centric nature ^[5]. The ever-increasing competition amongst the big brands in the beauty and cosmetics scene has fostered unprecedented innovation. However, innovation comes at an environmental cost ^[6].

The formulation of cosmetics is a major natural resource drainer. The beauty industry uses large quantities of raw materials that are either grown, harvested, or chemically synthesized in a laboratory. Many beauty products create a high demand for natural oils and plant essential oils, leading to excessive cultivation and over-exploitation of plantations, deforestation, and soil and water contamination. Extraction of fragrant molecules from natural sources can seriously burden the environment.

The comparatively higher price points of "sustainable" beauty products inadvertently position them as luxury. Yet, for anything to be truly sustainable, it needs to be equitable ^[7].

The price of “natural” comes from the amount of physical labour/physical effort that goes into production. Due to current environmental and safety considerations, there is a great need for sustainable and environmentally friendly production of high-value chemicals ^[8].

Indian Sandalwood is one such natural resource that has fallen into the traps of unsustainability caused by this industry and has become a threatened species…

Why sandalwood?

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In Indian culture and civilisations, sandalwood is significant in every aspect of human life, mainly serving roles from cradle to cremation, from ancient Indus Valley civilisation to the modern era . Beyond its spiritual significance, sandalwood has been India's aromatic ambassador to the world. Its alluring scent has captivated people across cultures, making it into soaps, cosmetics, and fragrances globally. The most prized variety, Santalum album (Indian Sandalwood), grows exclusively in peninsular India and ranks among the world's most valuable woods ^[9],[10].

What makes sandalwood genuinely extraordinary is its enduring fragrance. Unlike other aromatic woods, it retains its captivating scent for decades. The molecular structure of sandalwood oil's components is unique amongst perfumery’s woody notes. Sesquiterpenes α-santalol and β-santalol are primarily responsible for their fragrance, extracted from the tree’s heartwood via steam distillation. This essential oil fixates perfumes, providing a captivating and long-lasting base note ^[11].

Fig.3. Alpha and beta santalol are the major components of the sandalwood oil.

Sandalwood oil in cosmetic and perfumery

Indian sandalwood is favoured among all the species due to its high concentrations of α-santalol and β-santalol. Since its anti-ageing and anti-inflammatory qualities make it a vital component of many cosmetic goods, its oil is highly sought after and is imported mainly by the US and France. It is also highly valued in perfumery, offering a unique oriental, woody scent that enhances and preserves the aromatic qualities of other fragrance ingredients. The increasing use of sandalwood oil is driving its global production and consumption. Numerous beauty companies invest millions of rupees to acquire sandalwood as a raw material, underscoring its significance in the industry ^{[12],[13],[14]}.

Extraction of oil from wood

While sandalwood is highly popular all over the globe, the process of its oil extraction is equally an arduous and taxing job. An enormous amount of resources is spent to grow high-quality sandalwood trees, with the price contingent upon factors such as oil content, maturity of heartwood, and weight. It takes around 15 to 20 years for the trees to mature. They grow best in hot, humid climates. The tropical belt of peninsular India ideally comprises all required environmental conditions and is home to sandalwood trees ^[15]. Sandalwood is a root hemiparasite and relies on the host for minerals, nutrients, and water. It requires vast space for growth along with hosts to meet its nutrient requirements.

Its oil extraction typically involves hydrodistillation, steam-hydro distillation, or steam distillation, taking an enormous time of 40-70 hours. The process is usually halted when oil yield becomes economically inefficient. Investing a lot of resources, labour, and other inputs only to receive a small output contributes to the exorbitant price of sandalwood oil. Therefore, more efficient techniques are needed for maximum oil yield with minimal energy wastage ^[16].

High demand and Low supply

Owing to this precious wood’s growing preference and overexploitation by a consumer-centric industry, the supply now is too short to meet the demands! There is a demand for sandalwood to the tune of 20,000 metric tons, and its oil is estimated to be 1000 tons in the international markets. However, the supply was only in the past; Indian sandalwood had a monopoly in trade, and 90% of the supply was from India ^[17]. It was during the 1950s–1980s that massive overharvest and mismanagement by the post-colonial state-run sandalwood oil industry and other industries that use this oil brought the species to the brink of extinction. This crisis continues today as sandalwood stocks in India continue to decline alongside long-standing sectors ^[18].

To gain deeper insight into the situation, we interacted with the Divisional Forest Officer (DFO) of Marayoor Sandalwood Reserve, a critical bastion in India's efforts to preserve its dwindling sandalwood resources. In the wake of severe depletion in Karnataka and Tamil Nadu, Marayoor has become the epicentre of sandalwood production, necessitating a delicate balance between exploitation and preservation. During our talk, we learned about the extensive measures being taken to safeguard this valuable resource and the challenges faced, including overexploitation and wildlife conflicts. The present management system restricts the availability of sandalwood logs and oil to department-seized material and limited auctions, with Marayoor serving as the sole commercial sandalwood-selling location in India through a controlled auction system.
Explore our engagement with Karnataka Soaps and Detergents Limited (KS&DL), a prominent producer of sandalwood oil products in India, to gain insights into the market demand and export opportunities.

Indian Sandalwood was most recently assessed for The IUCN Red List of Threatened Species in 2018 and is listed as Vulnerable under criteria A2de ^[19],[20]. Recently, biotic interferences have also led to the depletion of the sandalwood growth in our country, and this problem is exacerbated by the illicit fellings and smuggling in natural plantations, causing the current price of oil to skyrocket.

The taxing job of oil extraction, unfulfilled global demands of sandalwood, and the unsustainability of the beauty industry leading to the sandalwood reserves nearing exhaustion are the primary reasons our team decided to explore solutions through synthetic biology.

Our project aims to synthesise sandalwood oil through genetically engineered bacteria using PET plastic as the feedstock. While the oil serves its purpose as both a raw material for multiple cosmetic products and as a direct end-consumer product in its pure form, we aim to focus on its subsequent use as a raw material for the beauty industry to provide them with a more sustainable and unique alternative that can potentially fulfil their demands and conserve the sandalwood population simultaneously along with its contribution towards fighting plastic pollution.

Plastic pollution: a never-ending pandemic

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Global plastic pollution has become a ubiquitous environmental problem. The unsustainable plastic production of the last decades, extensive use in consumer products, and waste mismanagement have resulted in increased global plastic pollution and subsequent degradation into micro(nano)plastics in the environment ^[21]. Polyethylene terephthalate (PET) is the third most widely diffused polymer exploited in the packaging industry, monopolising the beverage bottle market ^[22]. Due to its excellent transparency, lightweight, gas and water barrier properties, impact strength, UV resistance, and unbreakability (compared to a glass bottle), the production and use of PET bottles for beverage packaging has consistently increased worldwide ^[23].

The following analyses have highlighted the urgency to improve sustainable waste management practices.

Fig.4. Annual global plastic waste production ^[24],[25].

Fig.5. Annual plastic waste production in India ^[26].

PET can be recycled mechanically or chemically, but the higher costs of chemical recycling aren't justified when converting PET back to its original form. As a result, less than 30% of PET produced annually is recycled ^[27].

PET as feedstock

While there are various methods of plastic recycling, it is not a viable solution to help reduce plastic waste as it causes more loss and harm than good. There is also a strong economic incentive, with plastics losing 95% of their material value after a single use, leading to an estimated $110 bn loss to the global economy per annum ^[28]. Since we aim at sustainability, we decided to use PET plastic as feedstock to produce a value-added product like sandalwood oil, and we were inspired by Dr Joanna Sadler and Dr Stephen Wallace’s work on Microbial synthesis of vanillin from waste poly(ethylene terephthalate).

Owing to PET’s versatility and ease of use, its consumption has continuously increased, resulting in considerable waste generation. Currently, several physical and chemical recycling processes have been developed to address this problem. Circular repurposing of plastic materials is critical for building a socioeconomic ecosystem without contributing to plastic waste. Upcycling converts waste materials into products of greater worth and quality in their second life. Upcycling also helps achieve the circular economic feasibility of plastic waste with complete recyclability and no loss of value or usability, in contrast to other recycling methods ^[29],[30].

PET’s stability and resistance to hydrolytic or enzymatic degradation have led to PET being the most commonly found plastic waste in the environment. Recently, biological upcycling has been actively studied and has come to be regarded as a powerful technology for overcoming the economic issues associated with conventional recycling methods. Synthetic microbes offer a promising solution by supporting a circular materials economy, reducing energy and environmental impacts, and creating market incentives for PET reclamation ^[27],[29].
Research done by Sadler and Wallace is one of the first breakthroughs in the field of PET reclamation. Except for this work, there have been no examples of interfacing enzyme-catalyzed PET degradation with biological upcycling pathways to date.

Hence, to work on this issue, we aim to engineer bacteria to utilise the monomers and further synthesise value-added products like plant essential oil. While we focus on PET now in this project, this can also be taken further to other plastics as well. Explore our Proposed Implementation page to learn more.

PETal: Our solution

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The current scarcity of sandalwood trees and oil has no well-defined strategy to balance tree conservation and oil production, as one is destructive of the other process. To effectively overcome this shortage of sandalwood oil while ensuring a sustainable loop from PET waste generated, we wanted to design a modular system, PETal, that could achieve a net zero production of raw materials and valorising waste.

Polyethylene terephthalate (PET), a commonly used plastic, consists of Terephthalic acid (TPA) and Ethylene glycol (EG) as monomers. We have developed a synthetic biology module wherein plant essential oils can be produced by microbes feeding on PET monomers. By using an already available, engineered Pseudomonas putida that can metabolise and grow solely on TPA and EG as carbon sources ^[31],[32], we will be incorporating the santalol (Sandalwood Oil) synthesis pathway in this chassis for the first time to produce the oil components, Santalene and Santalol from TPA and EG.

The Approach

The engineered P. putida can solely take up TPA and EG from the environment and drive the central carbon metabolism within the bacteria ^[33]. We aim to direct this flux towards the native terpenoid synthesis pathway (MEP), followed by the Santalol Synthesis Pathway, through a holistic approach combining metabolic modelling and experimental design.

Fig.6. Our engineered pathway.

The novel aspect of this approach is the introduction of Santalol Synthesis Pathway through three enzymes, namely: 1) Farnasyl Pyrophosphate Synthase (FPPS), 2) Santalene synthase (SaSSy), and 3) Cytochrome P450 monooxygenase (P450) into the chassis.

Specifically, the expression of Cytochrome P450 in prokaryotic systems remains a profound challenge for the production of terpenoids large-scale, and through this project, we have theorised several experimental gene designs of the P450 that can potentially overcome this problem ^[34].

While experimentally, the introduction of pathway genes is straightforward, on the parallel, we will employ the Flux Balance Analysis to study the optimal growth conditions and fluxes and analyse the regulation of different pathways to get the desired end product ^[33]. FBA is a mathematical modelling technique to simulate biochemical reactions as a linear equation system in silico under the steady-state assumption. FBA allows us to analyse the pathways occurring in organisms, identify which reactions must be regulated for the end product, and suggest further optimisations concerning growth conditions and yield estimates.

As described above, the multifaceted approach allows us to create a microbial whole-cell synthesis system capable of utilising PET monomers and upgrading them into valued products, indicating a unified approach to PET upcycling. This project can be a pioneering step towards microbial factories synthesising plant secondary metabolites from plastic and can be extended to other essential oils with high therapeutic or fragrant properties.

Impact

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PETal holds significant potential for environmental benefits and positive impacts on society and the scientific community. Since these industries are natural resource-intensive, PETal aims to alleviate this burden on the sandalwood trees, a non-renewable resource, through a synbio solution. By shifting the focus from the oil extracted from trees to the oil produced through synbio, we can reduce the possibility of this species going extinct. In this way, our project can lend a hand towards the conservation of the threatened species. Moreover, the use of PET plastic as the feedstock to synthesise our desired product offers today’s world another route to plastic upcycling and, ultimately, helps tackle pollution.

The manufacture of several consumer products through synbio-production can potentially improve the sustainability of the industry. The conventional oil extraction method is time-consuming and resource-consuming. PETal cuts down several intermediate steps involved in traditional ways for procuring natural sandalwood oil, thus increasing efficiency and enabling us to meet the growing demand more rapidly. The production of alpha and beta-santalol can be industrial scaled up using well-regulated large-batch culture-type bioreactors followed by extraction and mixing to achieve the ideal composition, ensuring uniformity across batches ^[35]. In the USA and under European regulations (such as CFR 1990 and EEC 1334/2008), compounds derived from natural resources or produced through microbial or enzymatic processes using natural precursors are classified as "natural" (European Commission 2008; FDA 2013).
Synthetic biology and genetic engineering can open new doors for collaborating various consumer industries with biotech companies and potentially ignite the next industrial revolution.
Explore our Proposed Implementation page to learn more.

Our technology can revolutionise the synthesis of essential oils by putting forth a protocol to engineer/modify a bacteria to synthesise any plant essential oil and also ease the work of researchers by providing the parts required for modification.